About Michael Mullan Alzheimer Research

Please visit http://www.michael-mullan.com

Donation Campaign – 36 hour giving challenge campaign

 

Most of the Roskamp Institute’s funding comes from grant funding and the general public — people like you. Your gift makes a difference in the lives of people facing diseases such as Alzheimer’s Disease, Head Trauma, Drug Addiction, Cancer and Tourette’s Syndrome. Your contribution to the not-for-profit (501[c]3) Roskamp Institute is tax deductible and supports research to improve treatment and to ultimately develop a cure for these devastating diseases.

If you contribute to the Roskamp Institute by participating in the 36-Hour Giving Challenge at Giving Partner Challenge anytime between March 27 at 6 am and March 28 at 6 pm, your donation stands a great chance of being matched penny for penny.

Help us get a special grant for attracting the most donors. (We can win up to $20,000 by having the most unique donors give $25 or more to us.) Help us earn one of 20 grants for being among the first nonprofits to have 50 donors donate $50 or more.One random donor per hour will receive an additional $250 added to his/her donation. That could be you!You can help us get one of two $5,000 grants by visiting our profile on www.thegivingpartner.org during the challenge.

The Roskamp Foundation, a private foundation established by Bob and Diane Roskamp to administer all their philanthropic work in Sarasota and throughout the country. The Foundation has pledged to match all gifts to the Institute dollar for dollar that come in during the 36-Hour Giving Challenge, up to a maximum total of $50,000.

The money raised through the Giving Challenge will be used to further our research and will make a significant difference in the lives of people facing diseases such as Alzheimer’s Disease, head trauma, Gulf War Syndrome, Autism, drug addiction and Tourette’s Syndrome.

All donations must be made online. When you are ready to make your donation on March 27, go to www.GivingPartnerChallege.org, enter Roskamp in the box at the upper right where it says “Search for Organizations” and then click Search. You will then go to a page with the Institute’s information which you will click on and the donation form will appear.

However, you can make your pledge right now and you won’t have to get up at 6:00 a.m. Just click below:

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Thank you for your gift to the Roskamp Institute to help us continue our very important work. If you have any questions or if you would like to make your donation right now over the phone, please call me directly at 941-752-2949 extension 390.

To learn more about supporting Roskamp Institute, please contact:

Mr. Steve Klindt
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Roskamp Institute

2040 Whitfield Avenue,
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Phone: 941-752-2949 ext 390
Fax: 941-752-2948

Email: Steve Klindt

Anti-Tumoral Activity of a Short Decapeptide Fragment of the Alzheimer’s Abeta Peptide.

The inhibition of angiogenesis is regarded as a promising avenue for cancer treatment. Although some antiangiogenic compounds are in the process of development and testing, these often prove ineffective in vivo, therefore the search for new inhibitors is critical. We have recently identified a ten amino acid fragment of the Alzheimer Abeta peptide that is anti-angiogenic both in vitro and in vivo. In the present study, we investigated the antitumoral potential of this decapeptide using human MCF-7 breast carcinoma xenografts nude mice. We observed that this decapeptide was able to suppress MCF-7 tumor growth more potently than the antiestrogen tamoxifen. Inhibition of tumor vascularization as determined by PECAM-1 immunostaining and decreased tumor cell proliferation as determined by Ki67 immunostaining were observed following treatment with the Abeta fragment. In vitro, this peptide had no direct impact on MCF-7 tumor cell proliferation and survival suggesting that the inhibition of tumor growth and tumor cell proliferation observed in vivo is related to the antiangiogenic activity of the peptide. Taken together these data suggest that this short Abeta derivative peptide may constitute a new antitumoral agent.

or more information on the Roskamp Institute and Alzheimer’s please visit:

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Impaired orthotopic glioma growth and vascularization in transgenic mouse models of Alzheimer’s disease.

Alzheimer’s disease (AD) is the most common form of dementia among the aging population and is characterized pathologically by the progressive intracerebral accumulation of beta-amyloid (Abeta) peptides and neurofibrillary tangles. The level of proangiogenic growth factors and inflammatory mediators with proangiogenic activity is known to be elevated in AD brains which has led to the supposition that the cerebrovasculature of AD patients is in a proangiogenic state. However, angiogenesis depends on the balance between proangiogenic and antiangiogenic factors and the brains of AD patients also show an accumulation of endostatin and Abeta peptides which have been shown to be antiangiogenic. To determine whether angiogenesis is compromised in the brains of two transgenic mouse models of AD overproducing Abeta peptides (Tg APPsw and Tg PS1/APPsw mice), we assessed the growth and vascularization of orthotopically implanted murine gliomas since they require a high degree of angiogenesis to sustain their growth. Our data reveal that intracranial tumor growth and angiogenesis is significantly reduced in Tg APPsw and Tg PS1/APPsw mice compared with their wild-type littermates. In addition, we show that Abeta inhibits the angiogenesis stimulated by glioma cells when cocultured with human brain microvascular cells on a Matrigel layer. Altogether our data suggest that the brain of transgenic mouse models of AD does not constitute a favorable environment to support neoangiogenesis and may explain why vascular insults synergistically precipitate the cognitive presentation of AD.

or more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

http://www.michaelmullan.us

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Characterization and use of human brain microvascular endothelial cells to examine β-amyloid exchange in the blood-brain barrier. Bachmeier C, Mullan M, Paris D.

Alzheimer’s disease (AD) is characterized by excessive cerebrovascular deposition of the β-amyloid peptide (Aβ). The investigation of Aβ transport across the blood-brain barrier (BBB) has been hindered by inherent limitations in the cellular systems currently used to model the BBB, such as insufficient barrier properties and poor reproducibility. In addition, many of the existing models are not of human or brain origin and are often arduous to establish and maintain. Thus, we characterized an in vitro model of the BBB employing human brain microvascular endothelial cells (HBMEC) and evaluated its utility to investigate Aβ exchange at the blood-brain interface. Our HBMEC model offers an ease of culture compared with primary isolated or coculture BBB models and is more representative of the human brain endothelium than many of the cell lines currently used to study the BBB. In our studies, the HBMEC model exhibited barrier properties comparable to existing BBB models as evidenced by the restricted permeability of a known paracellular marker. In addition, using a simple and rapid fluormetric assay, we showed that antagonism of key Aβ transport proteins significantly altered the bi-directional transcytosis of fluorescein-Aβ (1-42) across the HBMEC model. Moreover, the magnitude of these effects was consistent with reports in the literature using the same ligands in existing in vitro models of the BBB. These studies establish the HBMEC as a representative in vitro model of the BBB and offer a rapid fluorometric method of assessing Aβ exchange between the periphery and the brain.

or more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

http://www.michaelmullan.us

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Depletion of CXCR2 inhibits γ-secretase activity and amyloid-β production in a murine model of Alzheimer’s disease.

Alzheimer’s disease (AD) is a neurodegenerative disorder that leads to progressive cognitive decline. Recent studies from our group and others have suggested that certain G-protein coupled receptors (GPCRs) can influence the processing of the amyloid precursor protein (APP). Earlier, we demonstrated that stimulation of a chemokine receptor, CXCR2, results in enhanced γ-secretase activity and in increased amyloid-beta (Aβ) production. Taken together, results obtained from in vitro studies indicate that therapeutic targeting of CXCR2 might aid in lowering Aβ levels in the AD brain. To better understand the precise function and to predict the consequences of CXCR2 depletion in the AD brain, we have crossed CXCR2 knockout mice with mice expressing presenilin (PS1 M146L) and APPsw mutations (PSAPP). Our present study confirms that CXCR2 depletion results in reduction of Aβ with concurrent increases of γ-secretase substrates. At the mechanistic level, the effect of CXCR2 on γ-secretase was not found to occur via their direct interaction. Furthermore, we provide evidence that Aβ promotes endocytosis of CXCR2 via increasing levels of CXCR2 ligands. In conclusion, our current study confirms the regulatory role of CXCR2 in APP processing, and poses it as a potential target for developing novel therapeutics for intervention in AD.

For more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

http://www.michaelmullan.us

www.rfdn.org

Selective antihypertensive dihydropyridines lower Aβ accumulation by targeting both the production and the clearance of Aβ across the blood-brain barrier.

Several large population-based or clinical trial studies have suggested that certain dihydropyridine (DHP) L-type calcium channel blockers (CCBs) used for the treatment of hypertension may confer protection against the development of Alzheimer disease (AD). However, other studies with drugs of the same class have shown no beneficial clinical effects. To determine whether certain DHPs are able to impact underlying disease processes in AD (specifically the accumulation of the Alzheimer Aβ peptide), we investigated the effect of several antihypertensive DHPs and non-DHP CCBs on Aβ production. Among the antihypertensive DHPs tested, a few, including nilvadipine, nitrendipine and amlodipine inhibited Aβ production in vitro, whereas others had no effect or raised Aβ levels. In vivo, nilvadipine and nitrendipine acutely reduced brain Aβ levels in a transgenic mouse model of AD (Tg PS1/APPsw) and improved Aβ clearance across the blood-brain barrier (BBB), whereas amlodipine and nifedipine were ineffective showing that the Aβ-lowering activity of the DHPs is independent of their antihypertensive activity. Chronic oral treatment with nilvadipine decreased Aβ burden in the brains of Tg APPsw (Tg2576) and Tg PS1/APPsw mice, and also improved learning abilities and spatial memory. Our data suggest that the clinical benefit conferred by certain antihypertensive DHPs against AD is unrelated to their antihypertensive activity, but rely on their ability to lower brain Aβ accumulation by affecting both Aβ production and Aβ clearance across the BBB.

or more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

http://www.michaelmullan.us

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Induction of drug efflux protein expression by venlafaxine but not desvenlafaxine.

Venlafaxine and its metabolite desvenlafaxine are serotonin-norepinephrine reuptake inhibitors currently prescribed for the treatment of depression. Previously, it was reported that venlafaxine is an inducer of MDR1, the gene responsible for P-glycoprotein (P-gp). The present study expanded upon these findings by examining the effect of venlafaxine and desvenlafaxine on the expression of both P-gp and the breast cancer resistance protein (BCRP) in human brain endothelial cells (HBMEC), an in vitro model of the blood-brain barrier (BBB). The HBMEC were treated for 1 h with various concentrations (500 nM to 50 µM) of venlafaxine and desvenlafaxine. Western blot analysis revealed treatment with venlafaxine significantly induced the expression of P-gp (2-fold) and BCRP (1.75-fold) in a dose-dependent manner, while treatment with desvenlafaxine had no effect on drug efflux transporter expression. To determine the functional significance of this effect, the permeability of a known drug efflux probe, rhodamine 123, across the BBB model and Caco-2 cells, a model of intestinal absorption, were examined. Treatment with venlafaxine (1-50 µM) for 1 h significantly reduced the apical-to-basolateral permeability of R123 across the BBB model (30%) and Caco-2 cell monolayers (25%), indicative of increased drug efflux transporter expression at the apical membrane. Conversely, desvenlafaxine had no effect on R123 permeability in either cellular model. These studies indicate that venlafaxine, but not desvenlafaxine is an inducer of drug efflux transporter expression, which consequently increases the potential for clinical drug-drug interactions. Therefore, based on these preliminary results, caution should be taken when prescribing venlafaxine with other P-gp substrates.

for more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

http://www.michaelmullan.us

www.rfdn.org

Selective dihydropyiridine compounds facilitate the clearance of β-amyloid across the blood-brain barrier.

Increasing evidence suggests that the soluble form of the β-amyloid peptide (Aβ) plays a critical role in the pathogenesis of Alzheimer’s disease. Previously, we reported that treatment with certain antihypertensive dihydropyridine (DHP) compounds can mitigate Aβ production in whole cells and reduce brain Aβ burden in a mouse model of Alzheimer’s disease. As Aβ clearance across the blood-brain barrier (BBB) is a key regulatory step in the deposition of Aβ in the brain, we examined the effect of DHP treatment on Aβ brain clearance. Treatment with certain DHP compounds significantly increased Aβ(1-42) transcytosis across the BBB in an in vitro model. The rank order of these compounds was nitrendipine>nicardipine=cilnidipine=lercanidipine>nimodipine>azelnidipine=nilvadipine. Conversely, amlodipine, felodipine, isradipine, and nifedipine had no effect on Aβ(1-42) BBB transcytosis. In an in vivo paradigm of Aβ clearance across the BBB, peripheral administration of nitrendipine, cilnidipine, and nilvadipine to wild-type animals facilitated the brain clearance of centrally administered exogenous Aβ(1-42), whereas with amlodipine, there was no effect. We also observed improved cognitive function in mice treated with nilvadipine following central Aβ(1-42) insult. Thus, in addition to the effect of certain DHP compounds on Aβ production, we demonstrate that certain DHP compounds also facilitate the clearance of Aβ across the BBB. This dual mechanism of action may be particularly effective in attenuating Aβ brain burden in Alzheimer’s disease and could open the door to a new class of therapies for the treatment of this disease.

for more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

http://www.michaelmullan.us

www.rfdn.org

Feasibility of Predicting MCI/AD Using Neuropsychological Tests and Serum β-Amyloid.

We examined the usefulness of brief neuropsychological tests and serum Aβ as a predictive test for detecting MCI/AD in older adults. Serum Aβ levels were measured from 208 subjects who were cognitively normal at enrollment and blood draw. Twenty-eight of the subjects subsequently developed MCI (n = 18) or AD (n = 10) over the follow-up period. Baseline measures of global cognition, memory, language fluency, and serum Aβ(1-42) and the ratio of serum Aβ(1-42)/Aβ(1-40) were significant predictors for future MCI/AD using Cox regression with demographic variables, APOE ε4, vascular risk factors, and specific medication as covariates. An optimal sensitivity of 85.2% and specificity of 86.5% for predicting MCI/AD was achieved using ROC analyses. Brief neuropsychological tests and measurements of Aβ(1-42) obtained via blood warrants further study as a practical and cost effective method for wide-scale screening for identifying older adults who may be at-risk for pathological cognitive decline.

for more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

http://www.michaelmullan.us

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Flavonoids lower Alzheimer’s Aβ production via an NFκB dependent mechanism.

Alzheimer’s disease (AD) is characterized by the brain accumulation of Aβ peptides and by the presence of neurofibrillary tangles. Aβ is believed to play an important role in AD and it has been shown that certain flavonoids can affect Aβ production. Recently, it was suggested that the Aβ lowering properties of flavonoids are mediated by a direct inhibition the β-secretase (BACE-1) activity, the rate limiting enzyme responsible for the production of Aβ peptides. Westernblots and ELISAs were employed to monitor the impact of flavonoids on amyloid precursor protein processing and Aβ production. A cell free chemoluminescent assay using human recombinant BACE-1 was used to assess the effect of flavonoids on BACE-1 activity. The effect of flavonoids on NFκB activation was determined by using a stable NFκB luciferase reporter cell line. Molecular docking simulations were performed to predict the binding of flavonoids to the BACE-1 catalytic site. Real time quantitative PCR was used to determine the effect of flavonoids on BACE-1 transcription. We show in a cell free assay that flavonoids are only weak inhibitors of BACE-1 activity. Docking simulation studies with different BACE-1 structures also suggest that flavonoids are poor BACE-1 inhibitors as they appear to adopt various docking poses in the active site pocket and have weak docking scores that differ as a function of the BACE-1 structures studied. Moreover, a weak correlation was observed between the effect of flavonoids on Aβ production in vitro and their ability to lower BACE-1 activity suggesting that the Aβ lowering properties of flavonoids in whole cells are not mediated via direct inhibition of BACE-1 activity. We found however a strong correlation between the inhibition of NFκB activation by flavonoids and their Aβ lowering properties suggesting that flavonoids inhibit Aβ production in whole cells via NFκB related mechanisms. As NFκB has been shown to regulate BACE-1 expression, we show that NFκB lowering flavonoids inhibit BACE-1 transcription in human neuronal SH-SY5Y cells. Altogether, our data suggest that flavonoids inhibit Aβ and sAPPβ production by regulating BACE-1 expression and not by directly inhibiting BACE-1 activity.

for more information on the Roskamp Institute and Alzheimer’s please visit:

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Roskamp Institute in Sarasota, Florida, have shown that an anatabine compound supplied by Rock Creek has beneficial effects on memory and learning in animal models of Alzheimer’s Disease. Michael Mullan, MD, Ph.D., CEO of the Roskamp Institute and his colleague, Dr. Daniel Paris, published these findings in October, 2011 in the European Journal of Pharmacology

A study released in the January 9th issue of the Journal of Neurology suggests that nicotine patches may help individuals with early memory loss. Dr. Paul Newhouse, a professor of psychiatry at Vanderbilt University Medical Center, led a study which showed that six months of nicotine patch treatment among patients who had mild cognitive impairment – often a precursor to Alzheimer’s disease – had a 46% improvement in their long-term memory for their age. The patient group who received a patch without nicotine showed a 26% decline in memory. Both patient groups were treated for six months.
Nicotine is only one of a family of related compounds known as alkaloids. Anatabine, another compound in the same family, has been actively pursued by Star Scientific for a variety of uses, including as a supporter for memory loss. Star Scientific subsidiary Rock Creek Pharmaceuticals also has a number of patents pending that relate to the administration of anatabine for treatment of a variety of neurological conditions, among other things.
Researchers at the Roskamp Institute in Sarasota, Florida, have shown that an anatabine compound supplied by Rock Creek has beneficial effects on memory and learning in animal models of Alzheimer’s Disease. Mike Mullan, MD, Ph.D., CEO of the Roskamp Institute and his colleague, Dr. Daniel Paris, published these findings in October, 2011 in the European Journal of Pharmacology. Dr. Mike Mullan has commented, “Anatabine may have several advantages over nicotine in the support of memory with aging. For instance, anatabine seems to have a longer half-life in the blood, which necessitates less frequent dosing, and has shown no abuse potential in animal screening. In addition, anatabine is able to lower amyloid levels in animal models of Alzheimer’s disease which become abnormally high as the disease progresses.” Dr. Mike Mullan also commented that the Roskamp Institute is actively pursuing the use of anatabine as a support for memory loss, and will be initiating human studies to explore further this potential role for anatabine.

Please see full press release at: Star Scientifi

Mike Mullan Alzheimer Researcher Comments on: Nicotine May Help Combat Memory Loss study by Dr. Newhouse

A recent study at Vanderbilt University Medical Center conducted by Dr. Paul Newhouse and colleagues suggests that Nicotine patches may be very beneficial in individuals with mild cognitive impairment (MCI). MCI is frequently regarded as a precursor to Alzheimer’s disease and is primarily of the type that demonstrates reduction in memory while most other functions remain intact. However, with time, MCI frequently progresses to Alzheimer’s disease and there are no known treatments that can obviate the eventual decline of one to the other. However, this recent study, using Nicotine patches for six months, has shown that individuals under the influence of Nicotine showed a 46% improvement in their “long-term memory” for their age while the placebo ground showed a 26% decline. Researchers at the Roskamp Institute have been examining an analogous compound, Anatabine. Anatabine is also a tobacco leaf-derived product, but, has no known carcinogen effects, nor does it seem to have any addictive potential according to studies at Harvard University. Anatabine has been shown by scientists at the Roskamp Institute to be beneficial in mitigating against memory decline in animal models of Alzheimer’s disease. In addition, studies with Anatabine show that amyloid protein, the causative agent in Alzheimer’s disease, is reduced in animal models of the disease and that this reduction parallels the improvement in memory seen with treatment with Anatabine. Anatabine has several potential advantages over the use of Nicotine for the treatment of memory. For instance, as mentioned above, Anatabine is not addictive and it has a longer half life in the blood, necessitating less frequent administration. Drs. Michael Mullan and Daniel Paris have published their findings in the European Journal of Pharmacology regarding the use of Anatabine in the animal models of Alzheimer’s disease.

The Roskamp Institute is a stand-alone, not-for-profit research facility located in Sarasota, Florida headed by Drs. Mike Mullan and Fiona Crawford.

http://news.yahoo.com/nicotine-may-help-combat-memory-loss-215902174.html#ugccmt-post-frm-container

 

http://www.michaelmullan.us

Identification of Plasma Biomarkers of TBI Outcome Using Proteomic Approaches in an APOE Mouse Model.

Abstract The current lack of diagnostic and prognostic biomarkers for traumatic brain injury (TBI) confounds treatment and management of patients and is of increasing concern as the TBI population grows. We have generated plasma proteomic profiles from mice receiving TBI by controlled cortical impact at either 1.3 mm or 1.8 mm depth, comparing these against those of sham injured-animals to identify plasma biomarkers specific to mild or severe TBI at 24 hours, 1 month, or 3 months post-injury. To identify possible prognostic biomarkers, we used apolipoprotein E (APOE)3 and APOE4 transgenic mice, which demonstrate relatively favorable and unfavorable outcomes respectively, following TBI. Using a quantitative proteomics approach (isobaric tagging for relative and absolute quantitation – iTRAQ) we have identified proteins that are significantly modulated as a function of TBI and also in response to the TBI*APOE genotype interaction, the latter representing potential prognostic biomarkers. These preliminary data clearly demonstrate plasma protein changes that are not only injury dependent but also interaction dependent. Importantly, these results demonstrate the presence of TBI-dependent and interaction-dependent plasma proteins at a 3-month time point, which is a considerable time post-injury in the mouse model, and will potentially be of significance for combat veterans receiving assessment at extended periods post-injury. Furthermore, our identification of clusters of functionally related proteins indicates disturbance of particular biological modules, which potentially increases their value beyond that of solitary biomarkers.

for more information on the Roskamp Institute and Alzheimer’s please visit:

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Anatabine lowers Alzheimer’s Aβ production in vitro and in vivo

Brain Aβ accumulation represents a key pathological hallmark in Alzheimer’s disease. In this study, we investigated the impact of anatabine, a minor alkaloid present in plants of the Solanacea family on Aβ production in vitro using a cell line overexpressing the human amyloid precursor protein (APP) and in vivo using a transgenic mouse model of Alzheimer’s disease. In vitro, anatabine lowers Aβ₁₋₄₀ and Aβ₁₋₄₂ levels in a dose dependent manner and reduces sAPPβ production without impacting sAPPα levels suggesting that anatabine lowers Aβ production by mainly impacting the β-cleavage of APP. Additionally, we show that anatabine lowers NFκB activation at doses that inhibit Aβ production in vitro. Since NFκB is known to regulate BACE-1 expression (the rate limiting enzyme responsible for Aβ production), we determined the impact of anatabine on BACE-1 transcription. We show that anatabine inhibits BACE-1 transcription and reduces BACE-1 protein levels in human neuronal like SHSY-5Y cells suggesting that the Aβ lowering properties of anatabine are mediated via a regulation of BACE-1 expression. In vivo, we show that an acute treatment with anatabine for four days significantly lowers brain soluble Aβ₁₋₄₀ and Aβ₁₋₄₂ levels in a transgenic mouse model of Alzheimer’s disease. Altogether our data suggest that anatabine may represent an interesting compound for regulating brain Aβ accumulation.

for more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

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Elevated CSF levels of TACE activity and soluble TNF receptors in subjects with mild cognitive impairment and patients with Alzheimer’s disease.

Expression levels of tumor necrosis factor (TNF) receptors, TNFR1 and TNFR2, are significantly changed in the brains and cerebrospinal fluid (CSF) with Alzheimer’s disease (AD). Moreover, we also found that, in an Alzheimer’s mouse model, genetic deletion of TNF receptor (TNFR1) reduces amyloid plaques and amyloid beta peptides (Aβ) production through β-secretase (BACE1) regulation. TNF-α converting enzyme (TACE/ADAM-17) does not only cleave pro- TNF-α but also TNF receptors, however, whether the TACE activity was changed in the CSF was not clear. In this study, we examined TACE in the CSF in 32 AD patients and 27 age-matched healthy controls (HCs). Interestingly, we found that TACE activity was significantly elevated in the CSF from AD patients compared with HCs. Furthermore, we also assayed the CSF levels of TACE cleaved soluble forms of TNFR1 and TNFR2 in the same patients. We found that AD patients had higher levels of both TACE cleaved soluble TNFR1 (sTNFR1) and TNFR2 (sTNFR2) in the CSF compared to age- and gender-matched healthy controls. Levels of sTNFR1 correlated strongly with the levels of sTNFR2 (rs = 0.567-0.663, p < 0.01). The levels of both sTNFR1 and sTNFR2 significantly correlated with the TACE activity (rs = 0.491-0.557, p < 0.05). To examine if changes in TACE activity and in levels of cleaved soluble TNFRs are an early event in the course of AD, we measured these molecules in the CSF from 47 subjects with mild cognitive impairment (MCI), which is considered as a preclinical stage of AD. Unexpectedly, we found significantly higher levels of TACE activity and soluble TNFRs in the MCI group than that in AD patients. These results suggest that TACE activity and soluble TNF receptors may be potential diagnostic candidate biomarkers in AD and MCI.

for more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

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Genetic deletion of TNF receptor suppresses excitatory synaptic transmission via reducing AMPA receptor synaptic localization in cortical neurons.

The distribution of postsynaptic glutamate receptors has been shown to be regulated by proimmunocytokine tumor necrosis factor α (TNF-α) signaling. The role of TNF-α receptor subtypes in mediating glutamate receptor expression, trafficking, and function still remains unclear. Here, we report that TNF receptor subtypes (TNFR1 and TNFR2) differentially modulate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) clustering and function in cultured cortical neurons. We find that genetic deletion of TNFR1 decreases surface expression and synaptic localization of the AMPAR GluA1 subunit, reduces the frequency of miniature excitatory postsynaptic current (mEPSC), and reduces AMPA-induced maximal whole-cell current. In addition, these results are not observed in TNFR2-deleted neurons. The decreased AMPAR expression and function in TNFR1-deleted cells are not significantly restored by short (2 h) or long (24 h) term exposure to TNF-α. In TNFR2-deleted cells, TNF-α promotes AMPAR trafficking to the synapse and increases mEPSC frequency. In the present study, we find no significant change in the GluN1 subunit of NMDAR clusters, location, and mEPSC. This includes applying or withholding the TNF-α treatment in both TNFR1- and TNFR2-deleted neurons. Our results indicate that TNF receptor subtype 1 but not 2 plays a critical role in modulating AMPAR clustering, suggesting that targeting TNFR1 gene might be a novel approach to preventing neuronal AMPAR-mediated excitotoxicity.-He, P., Liu, Q., Wu, J., Shen, Y. Genetic deletion of TNF receptor suppresses excitatory synaptic transmission via reducing AMPA receptor synaptic localization in cortical neurons.

for more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

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Proteomic CNS profile of delayed cognitive impairment in mice exposed to gulf war agents.

Gulf War Illness (GWI) is a chronic multisymptom condition with a central nervous system (CNS) component, for which there is no treatment available. It is now believed that the combined exposure to Gulf War (GW) agents, including pyridostigmine bromide (PB) and pesticides, such as permethrin (PER), was a key contributor to the etiology of GWI. In this study, a proteomic approach was used to characterize the biomolecular disturbances that accompany neurobehavioral and neuropathological changes associated with combined exposure to PB and PER. Mice acutely exposed to PB and PER over 10 days showed an increase in anxiety-like behavior, psychomotor problems and delayed cognitive impairment compared to control mice that received vehicle only. Proteomic analysis showed changes in proteins associated with lipid metabolism and molecular transport in the brains of GW agent-exposed mice compared to controls. Proteins associated with the endocrine and immune systems were also altered, and dysfunction of these systems is a prominent feature of GWI. The presence of astrogliosis in the GW agent-exposed mice compared to control mice further suggests an immune system imbalance, as is observed in GWI. These studies provide a broad perspective of the molecular disturbances driving the late pathology of this complex illness. Evaluation of the potential role of these biological functions in GWI will be useful in identifying molecular pathways that can be targeted for the development of novel therapeutics against GWI.

for more information on the Roskamp Institute and Alzheimer’s please visit:

http://www.mullanalzheimer.com

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Institute targets in on Alzheimer’s

May 7, 2007 – At St. James Hospital in Dublin, Ireland, a nurse is checking the blood pressure of a 62-year-old man. Later, a tech will use a hand-held scanner to measure blood flow in his middle cerebral artery.

The patient has never met Michael Mullan, nor Fiona Crawford. But some 4,150 miles away, they could hardly be happier about his test results.

They show that the man, whose identity is confidential, is showing no adverse reactions to a drug that might be a promising treatment for Alzheimer’s disease.

That is good news for Mullan and Crawford. Directors of the Roskamp Institute, on Whitfield Avenue in southern Manatee County, they are running a clinical trial of Nilvadipine, a drug widely used abroad but not approved in the United States.

The drug is intended to lower blood pressure. But in studies on mice, Roskamp researchers found it also reduced the level of a protein in the brain believed to be at the heart of Alzheimer’s.

The Ireland trial just completed its second phase, a safety study, and the 20 patients taking the drug showed almost no ill effects, paving the way for a broader study.

The clinical trial is the institute’s highest-profile project, but its two dozen scientists also work in fields including drug addiction and head injury.

With even more promising treatments deep in its labs, the little nonprofit academic center is becoming more and more a biotechnology start-up.

Birth of the institute

The institute was born in 1997, but its origins date back another 40 years.

Bob Roskamp was a high school physics teacher. His older brother, diagnosed with schizophrenia, killed himself.

Roskamp tells the story with understatement: “Obviously, it catches your attention in a big way.”

The loss of his brother prompted him to give up teaching and work on opening homes for developmentally disabled adults. He later moved into developing housing communities for seniors.

He began selling his companies — including his Freedom Group to American Retirement Group for $23 million in cash and $14.9 million in stock — leaving him with a question: “What do we do with these surplus dollars?”

The answer is in the logo of the institute bearing his name: “Curing Diseases of the Mind.”

Roskamp and his wife, Diane, are among the pioneers of a style of philanthropy, now more widely followed, of carefully aiming resources at one target and tracking performance.

“Instead of spreading it thinly throughout the world, we would ‘rifle-shot’ it, and have a lot more fun with it,” he said.

Roskamp historically has given the institute about one-third of its operating budget, the rest coming through grants and contracts.

But as federal money has been diverted elsewhere, and the institute’s work has grown more complex, Roskamp has had to pick up more of the tab. He gave just over $1 million in 2005, but $4.6 million this year, he said.

His involvement began with funding a lab at the University of South Florida, then a teaching position eventually filled by Mullan.

In 2003, the institute left the university amid personnel and bureaucratic disputes and moved into the former Bausch & Lomb building in southern Manatee County. Roskamp said university overhead was too expensive, and that scientists can work faster in the independent setting.

“You bring your entrepreneurial hat to this kind of research,” he said. “We’re results-oriented people.”

The scientists appreciate not having to wait for grants and approvals.

“We have the funding from Bob and Diane that allow us to move forward very quickly when we make a new discovery,” Crawford said. “We are really free to focus on the research.”

Paddling mice

Most Alzheimer’s researchers now focus on a protein known as beta-amyloid that forms when a chemical process goes awry. The protein clumps together outside neurons, eventually killing those memory cells.

Mullan and Crawford were part of a team that in 1991 published papers establishing a link between a human gene, on chromosome 21, and early onset of the disease in patients in their 40s and 50s.

A year later, after they came to the United States, they published a paper looking at another genetic link to early-onset Alzheimer’s.

The research made beta-amyloid a prime suspect in Alzheimer’s, and stopping its buildup a potential cure.

Roskamp researchers look for existing drugs and new compounds with that effect. Nilvadipine showed enough promise to test it on lab mice engineered to have Alzheimer’s.

At 10 months, with the disease in full bloom, some mice got the drug while others got a placebo. Later, they scanned the mice’s brains for blood flow.

In the color-coded pictures, the brighter the image, the better the blood flow. The mice getting Nilvadipine scan largely red and orange.

The control animals scan mostly blue-green.

Mullan points to a chart with results of a more traditional test, tracking a mouse’s effort to paddle its way out of a mouse-sized swimming pool.

The mice repeat the test, day after day. Normal mice figure it out and eventually swim a shorter route to the exit.

Mice with Alzheimer’s disease never figure it out, actually taking longer and longer routes.

“But if you give them Nivaldipine, they go from here to here; they do better,” Mullan said, pointing at the figures. “And if you give Nilvadipine to a normal mouse, they do best of all.”

The drug appears to slow or stop the production of beta-amyloid, Mullan said.

As the brain grudgingly yields the mysteries of its architecture, Roskamp’s scientists are exploring how those diseases of the mind may be related by more than just words.

‘Blocking that burst’

In 2002 the institute teamed with the Department of Veterans Affairs to look at memory skills in people who had received traumatic brain injuries.

They found that people who had a gene linked to Alzheimer’s disease recovered less memory function than those without it, even when they had comparable injuries and demographics.

Further research has shown that when the brain suffers such an injury, there is a burst of amyloid production. One theory is that the brain produces the protein as a defense mechanism, but it sometimes overreacts and makes matters worse.

“Blocking that burst appears to be at least one way to try and improve outcomes after head injury,” said Crawford, lead author of the 2002 article.

Last year the Department of Defense approved a $1.5 million grant to the institute to expand that research. It is a particularly urgent matter for the military: Improved body armor is helping soldiers survive explosions — but with little-understood head injuries.

“People can have brain injury even if they didn’t suffer any loss of consciousness, weeks and months of being in the vicinity of an explosive attack,” Crawford said.

For now, that grant is hung up in final reviews.

“We have yet to see dime one,” Roskamp said — but even that $1.5 million pales in comparison with the costs of the Nilvadipine study.

That cuts to the heart of the dilemma scientists face. They might get a moderately effective drug to market quickly, or try to discover the “silver bullet,” which could take many years and exponentially more money.

Roskamp is preparing the foundation to do both.

Just a question of when

To Mullan, the question is not whether there will be treatments for Alzheimer’s.

“It’s the question of when we’re going to get them there,” he said.

It is a question of how effective they will be. Mullan cited three drugs far along in the pipeline, all targeted at reducing amyloid. “They’re not going to be block-busting, perfect drugs by any means, but I think at least two of them will be approved for Alzheimer’s this year.”

Nilvadipine most likely would be like them — useful but not the cure-all. But it offers some advantages.

Developing a new drug from scratch is a much worse bet, Mullan said. Count on 10 to 12 years for development, testing and approvals, with a high failure rate.

“Sometimes they fail spectacularly,” he said, citing Vioxx, a promising drug with unforeseen and deadly side effects.

Nilvadipine, in use for more than a decade, already has a track record for safety. It could help patients while allowing the institute time to find the silver bullet.

By mid-year, the institute hopes to continue the Ireland trial with a double-blind study, meaning neither patients nor doctors know who gets Nilvadipine and who gets a placebo until they conclude. That study, which would involve about 200 people, could cost $20 million, Roskamp said.

Should the drug prove effective, Nilvadipine’s manufacturer could profit — but so would the institute. Because it holds rights to the drug’s newly indicated use, the institute would receive royalty payments, Roskamp said.

The institute has set up a for-profit subsidiary, Roskamp Research LLC, which holds its patents. Roskamp structured it to allow outside backers to support studies, provide the subsidiary with a return on its investment, and guarantee most of the revenue goes to his institute.

“We don’t want to give it to a pharma company, and say here, go make a lot of money off of it,” Roskamp said.

Compounds back in the institute’s labs could provide better returns — and better treatments.

Sarasota’s Roskamp Institute Releases Study Defining a Mechanism for Development of Obesity and the Metabolic Syndrome, Forerunners of Type 2 Diabetes

Sarasota, Fla. – August 1, 2007 The Roskamp Institute released a study defining a mechanism for the development of obesity and the metabolic syndrome, which are the forerunners of type 2 diabetes.  The study, led by Roskamp’s Dr. Robert Farese, is detailed in the August issue of The Journal of Clinical Investigation, a highly prestigious medical research journal.

 

While the Roskamp Institute’s primary focus is on Alzheimer’s disease, Roskamp researchers have a significant interest in diabetes due to studies that suggest those who have diabetes are more likely to develop Alzheimer’s disease.

 

The study found that a deficiency in an enzyme, atypical protein kinase C, impairs the ability of insulin to stimulate glucose uptake into the muscle, which produces a state of resistance to circulating insulin.  Once this occurs, the liver begins to produce excessive quantities of fat, causing abdominal obesity and alterations in blood lipids.  According to the study, this can then lead to obesity and the metabolic syndrome, the precursors of type 2 diabetes.

 

“Although this gene-knockout study was done on mice, it is particularly relevant to type 2 diabetic humans, who are known to have deficiencies of this enzyme in their muscles,” said Dr. Farese.  “The findings showed that in the mice a simple loss of one or more genes that are responsible for the production of this enzyme could eventually cause obesity and the metabolic syndrome which then could lead to type 2 diabetes.”

 

Further research must be done to determine how human diabetics acquire a deficiency of this enzyme in their muscles; however, this mouse model should be especially helpful to further study and devise treatments for obesity and the metabolic syndrome.

 

“We are particularly excited about this study and the potential to develop treatments for obesity and the metabolic syndrome, which are both global health problems,” said Dr. Michael Mullan, director of the Roskamp Institute.  “This study will also be helpful in further determining how obesity, the metabolic syndrome and type 2 diabetes are linked to Alzheimer’s disease.”

 

The study was co-authored by Dr. Farese, who led the team of Mini P. Sajan, Hong Yang, and Sonali Nimal at the Roskamp Institute; and others at the James A. Haley Veterans Administration Medical Center in Tampa; the University of South Florida College of Medicine; the Joslin Research Foundation and Harvard University School of Medicine; Yale University School of Medicine, and Research Center at Oslo, Norway.

 

For more information regarding this study or the Roskamp Institute please visit:

 

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

www.rfdn.org

The Roskamp Institute

The Roskamp Institute, a not-for-profit research Institute, is dedicated to finding cures for neuropsychiatric disorders, with the emphasis on Alzheimer’s disease (AD).  Current research at the Roskamp Institute is focused on dissecting the molecular biological pathways implicated in AD pathogenesis in order to develop therapeutic targets specific to AD etiology. Dr. Michael Mullan (Director of the Roskamp Institute) and Fiona Crawford (Associate director of the Roskamp Institute) were part of the original team that discovered a genetic error called the “Swedish mutation” which results in overproduction of  b-amyloid (Ab) by aberrant proteolytic processing of the amyloid precursor protein (APP). This mutation now forms the bases of most mouse model of Alzheimer’s disease. Previously, the Roskamp Institute published an article in a prestigious scientific journal, Nature, showing that Ab plays a normal role in vasoactive mechanisms but also plays a role in vascular abnormalities and neurodegeneration mediated by free radical. Subsequently, Dr. Daniel Paris, a senior scientist at the Roskamp Institute, discovered that the vasoactive effects of Ab are partly mediated via a pro-inflammatory pathway and showed that this effect of Ab on the vasculature can be blocked by inhibiting specific target molecules.  In order to further understand the role of Ab in the vasculature, Dr. Paris investigated the long term effect of Ab on vascular homeostasis. He then discovered that at low doses, Ab promotes angiogenesis, while at high doses, certain forms of Ab peptides are anti-angiogenic. Collectively, these novel findings resulted in new therapeutic prospects for the treatment of Alzheimer’s disease as well as Cancer.

Researchers at the Roskamp Institute also showed that the presence of functional CD40/CD40L signaling is essential for the full development of AD like pathology in transgenic mouse models of AD. In particular, it was demonstrated that accumulation of cerebral Ab is reduced in transgenic mouse models of AD by genetically or pharmacologically reducing the availability of CD40L to CD40. The Roskamp Institute investigators subsequently revealed that loss of functional CD40L diminishes both APP processing to Ab and microglial activation in the brain (Original findings published in journals Science and Nature Neuroscience). CD40L activated pathways in the presence of Ab appear to mediate both of these effects as well as the hyperphosphorylation of murine tau in vivo at epitopes analogous to those which precede tangle formation of human tau. More recently, Dr. Ghania Ait-Ghezala of the Roskamp Institute showed that CD40/CD40L interaction also affects APP via the NF-kB pathway. Using NF-kB inhibitors and SiRNAs to silence diverse elements of the NF-kB pathway, she demonstrated that reduction in levels of both pathological forms of Ab. These results showed that CD40L stimulation may be a key component in AD pathology and that NF-kB pathway may be suitable targets for therapeutic approaches against AD.

Another major focus of research at the Roskamp Institute includes Traumatic Brain Injury (TBI) Program headed by the Associate Director of the Roskamp Institute. Dr. Crawford and her Roskamp Institute team demonstrated an important relationship between apolipoprotein E (APOE) and memory following TBI. She demonstrated that in Veteran’s with TBI, memory performance was significantly worse in individuals who had at least one copy of APOE ε4 allele than those who did not. She had subsequently been funded through the Veteran’s Administration to further study the relationship between different forms of APOE in TBI with the emphasis on finding treatments for this devastating condition.

Drs. Michael Mullan and Fiona Crawford also received funding by the Counterdrug Technology Assessment Center (CTAC) to evaluate the newly emerged genomics and proteomics technology and find biological markers of substance abuse. Recently, Dr. Crawford’s team showed that cocaine treatment of human progenitor neuronal cells results in increased oxidative stress (possibly mediated by inflammatory responses) which precedes cell death. Thus, these findings may have implications for the consequences of cocaine abuse in situations where antioxidant capacity is compromised, as in the aging brain.

As evident here, the Roskamp Institute team has been a pioneer in many area of research in neuropsychiatric diseases and will continue to do so to find novel therapies for these disorders. Currently, a new clinical trial based on the discoveries made at the Roskamp Institute is underway to assess safety and efficacy of nilvadipine in treatment of Alzheimer’s disease. Through the generous support of Diane and Robert Roskamp, the Veteran’s Administration, the National Institutes of Health, CTAC and the Department of Defense, the Roskamp Institute will continue to provide potential avenues for novel therapeutic interventions for neuropsychiatric disorders.

 

for more information on the Roskamp Institute please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

www.rfdn.org

Roskamp Institute on Gulf War Illness

The Roskamp Institute located in Sarasota, Florida is the leading research center in the area.  The research focuses on neurological diseases that affect young and elderly men and women of this world. Some of the main focuses are Alzheimer’s disease, addiction, post-traumatic stress disorder (PTSD), multiple scoliosis, Gulf War syndrome and many more. The Director Dr. Michael Mullan leads his team of researchers to exciting findings. Recently the Institute has been given a grant from the VA for their research involving Gulf War Illness. This Illness that inflicts the soldiers that fought during the Gulf War affects their motor skills, memory, stability and other problematic symptoms. How the Illness commenced was through the combination of the neurotoxins and pesticides given to the soldiers. The research done in the Institute led to the finding that shows the toxic mixture affects the long fatty acid chains within the brain. Research continues within the walls of the 42,000 sq. ft research facility hopefully terminating the life altering Illness for our Veterans.

 

for more information on the Roskamp Institute please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

www.rfdn.org

The Roskamp Institute Battles Drug Abuse

A National Survey on drug abuse in America reported in 2004 that about 34 million Americans are currently using or have been exposed to cocaine at some point in their lifetime. Cocaine is highly addictive and affects individuals along with their families. The cost of health care services has risen due to the increasing use of cocaine. Currently, the Roskamp Institute is involved in research to discover a treatment for substance abuse. Dr. Michael Mullan MD, PhD is the director of the Roskamp Institute and has worked vigorously on addiction and has found that addictive disorders have a significant genetic component. These genetic components play a key role in drug abuse.

The Roskamp Institute scientists have previously shown that a genetic change called polymorphism in a gene for an opioid receptor in the brain is a risk factor for alcohol dependency. With this information, the Roskamp Institute researchers then examined the frequencies of this polymorphism carrying genotypes and alleles in numerous groups of individuals addicted to the substance versus individuals with no history of addiction to the substance. These Roskamp Institute scientists found that the mu-opioid receptor’s polymorphism is a genetic risk factor for substance dependence but not to any particular type of drug. Meaning, an individual with this polymorphism is more likely to become addicted to a substance than an individual without it. The Roskamp Institute previously published these findings in the journal Molecular Psychiatry.

Dr. Mullan and Dr. Crawford along with the other researchers at the Roskamp Institute received an award from the Counter drug Technology Assessment Center (CTAC), to continue their work on drug addiction.

Affymetrix is a name of the company which provides the Roskamp Institute with the genetic software that is used by scientists who study genetics (genomics). The Roskamp Institute used genomics technology in order to find the cocaine’s affects on the brain cells known as neuronal cells.  The Roskamp Institute scientists continue to research projects which are focused on the inflammatory and immune responses to cocaine.  The Roskamp Institute scientists showed that these responses also results from the exposure of the neuronal cells to cocaine and these responses are also time dependant. These findings, originally published in the Journal of Neurochemistry, illustrate that there are biological and physical consequences of cocaine addiction.

The Roskamp Institute researchers are currently working on studies involving oxidative stress in the brain.  This oxidative stress can also be caused by excessive use of cocaine and is hypothesized to result in permanent brain damage.  With such experiments in progress, the Roskamp Institute is a good candidate for additional government funding and  these discoveries will be useful towards the battle against drug abuse in form of treatments.

The Traumatic Brain Injury Program at the Roskamp Institute

Among the soldiers who survive conflicts in Iraq and Afghanistan, the traumatic brain injuries account for a larger proportion of their casualties than in any other US war in recent history. According to the Joint Theater Trauma Registry, established by the U.S. Army Institute of Surgical Research, approximately 22 percent of the injured US soldiers received injuries to the head, face, or neck. A major reason for this high ratio of these injuries is Kevlar body armor and helmets. Although, it successfully protects these soldiers from bullets and shrapnel exposure,Kevlar helmets cannot fully protect theface, head, and neck areas. Additionally, it is also unsuccessful in preventing the closedbrain injuries produced by blasts. Furthermore, among patients evaluated at Walter Reed hospital, closed head injuries outnumber other penetrating injuries (originally published in New England Journal of Medicine).

Most individuals with a mild traumatic brain injury improve entirely within a year,but moderate and severe brain injuries are more complex and have long-term consequences. The Center of disease Control and Prevention estimated that 5.3 million Americans are living with disabilities resulting from traumatic brain injury. Dr. Michael Mullan (Director of the Roskamp Institute) Dr. Fiona Crawford (Associate Director of the Roskamp Institute) and their team of scientists previously demonstrated that apolipoprotein E (APOE) influences traumatic brain injury outcomes. These Roskamp Institute scientists examined 110 participants from the Defense and Veterans’ Head Injury Program to determine a relationship between APOE genotype and memory performance on certain cognitive tests administered to these head injured soldiers. The memory performance was much worse in soldiers who had at least had one APOE epsilon 4 allele compared to those who did not. This Roskamp Institute team also determined that these findings were limited to memory and not other cognitive performances such as executive functioning. Therefore, these data support a specific role for the APOE protein in memory outcome following TBI, and suggest an APOE isoform-specific effect on neuronal repair processes (originally published in the journal Neurology).

Dr. Fiona Crawford received a Merit award from the Veteran’s Administration to further study, using genomics technology, the role of APOE in Traumatic Brain Injury. Dr. Fiona Crawford and her Roskamp Institute team have now completed the experiments showing differences in genomics response among the different mouse models after traumatic brain injury.  Recently, Drs. Michael Mullan and Fiona Crawford received a prestigious award of $1.5 million from the Department of Defense which will allow the Roskamp Institute to investigate ApoE and other proteins to find potential peripheral biological markers and novel therapeutic treatments for traumatic brain injury. Florida Senator Bill Nelson recently toured the Roskamp Institute to observe its traumatic brain injury program in support of the soldiers affected by this devastating condition.

The Roskamp Institute is a world-renowned state-of-the-art research and clinical facility located in Sarasota Florida dedicating to finding novel therapeutics for treatment of neuropsychiatric disorder, especially Alzheimer’s disease, traumatic brain injury and substance abuse. The Roskamp Institute is supported by the funding from government agencies such the National Institutes of Health, the Veteran’s Administration and the Department of Defense as well as private donations from the Robert and Diane Roskamp Foundation.

for more information on Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

www.rfdn.org

Roskamp Institute finds one of the genetic causes for Tourettes syndrome

Tourette syndrome (TS) is a heterogeneous childhood disorder and occurs with a frequency of approximately four to ten per 10,000 in the general population (Mason et al. 1998). The symptoms for Tourette syndrome include multiple motor and one or more vocal tics. These symptoms appear to overlap with other neurobehavioral disorders such as obsessive-compulsive disorder, attention deficit/hyperactivity disorder, mood disorders and learning disorders. The origin of Tourette syndrome is not clearly understood at this time. However, there appears to be presence of a genetic component, evidence for which comes from both family and twin studies. Furthermore, a complex mode of inheritance has been suggested which probably involves several genes with different effect size.  Additionally, environmental factors such as prenatal and birth complications may also influence the disease manifestation.

The Roskamp Institute scientists Drs. Michael Mullan (Director of the Roskamp Institute), Fiona Crawford (Associate Director of the Roskamp Institute) and Ghania Ait-ghezala (a senior scientist at the Roskamp Institute) have previously shown that among patients diagnosed with Tourettes syndrome in two unrelated families, there appears to be a breakage and translocation on chromosome 8 (original findings published in the journal Human Genetics).  Drs. Fiona Crawford and Ghania Ait-ghezala subsequently received funding from the Tourettes syndrome association to further characterize this chromosomal breakage.

Currently, there is no treatment available for Tourettes syndrome. Although, the symptoms in most individuals improve by the late teens and early 20s, this disorder is generally lifelong and chronic.  Studies have also shown that although symptoms such as tics may disappear after the childhood period, it is possible that other psychiatric disorders such as depression, panic attacks, mood swings, and antisocial behaviors persist and cause lifelong impairment in adults.  Therefore, a treatment for this disorder is much needed so that a child can actually be disease free throughout his/her life and has a decent chance of living a normal life. The Roskamp Institute is currently engaged in molecular biological research aimed at determining the genes that are disturbed when this chromosomal breakage and translocation occur. Through this novel finding, the scientists at the Roskamp Institute hope to discover a treatment for Tourettes syndrome.

The Roskamp Institute is located in Sarasota Florida and is a not-for-profit stand alone research institute dedicated to finding cures for neuropsychiatric disorders. The Roskamp Institute is currently conducting a clinical trial evaluating safely and efficacy of nilvadipine for the treatment for Alzheimer’s disease (clinical trial being performed in Dublin, Ireland). Furthermore, the Roskamp Institute is conducting various molecular biological studies to find treatment for chronic diseases such as cancer, diabetes, and other neuropsychiatric disorders such as traumatic brain injury, gulf war syndrome, and substance abuse. The Roskamp Institute operates two memory disorder clinics located in Sarasota and Tampa, Florida. These clinics conduct diagnostic assessments for memory disorders and conduct industry and government funded clinical trials in several neurological and neuropsychiatric disorders. The Roskamp institute is currently funded by the National Institutes of Health, the Veteran’s Administration, the Department of Defense and the private donation by the Robert and Diane Roskamp foundation. For more information or the research or clinical trials, please contact us at 94-752-2949.

Sarasota’s Roskamp Institute Welcomes U.S. Senator Bill Nelson

August 21, 2007

Sarasota, Fla. – The Roskamp Institute today welcomed U.S. Senator Bill Nelson to its research facility in Sarasota, Florida, where the Senator toured the laboratories and discussed the various types of research currently being conducted at the Institute.

 

“We thank Senator Nelson for his interest in our research and for coming to the Institute to tour our lab and view our good work first hand,” said Dr. Michael Mullan, director of the Roskamp Institute.  “We are proud of the research our Institute has done and look forward to continuing in our quest to better understand and ultimately cure debilitating diseases of the mind.”

 

While Senator Nelson’s visit was mainly to discuss with the researchers the current and future research being done in relations to Traumatic Brain Injury, the Roskamp Institute is devoted to understanding the causes of and finding cures for various neuropsychiatric and neurodegenerative disorders and addictions.  Specifically, the Institute utilizes a broad range of scientific approaches to understand the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease.

 

“We currently have 45 scientists and 10 clinicians with eight active clinical trials in the field with several more on the horizon,” Dr. Mullan continued.  “It is vital that we are persistent in our pursuit to help Florida’s sufferers and their families and we are glad Senator Nelson is here to share in our goal.”

 

The Roskamp Institute has built its esteemed reputation amongst the research community and has been heralded for its achievements including:

 

  • Being the first Florida-based Alzheimer’s Research Institute (and one of only a handful of Institutes worldwide) to conduct a human clinical trial with a drug discovered by its own research.
  • Discovering a new class of drugs that lower the production of the main pathological protein that causes Alzheimer’s disease.
  • Applying state of the art technologies (proteomics and genomics) to find early diagnostic markers for Alzheimer’s disease.

Extensive participation from Florida residents in the Institute’s leading edge Alzheimer’s research program.

for more information on Alzheimer’s please visit:

http://www.mullanalzheimer.com

http://www.mullanalzheimer.info

www.rfdn.org

Dr. Mullan’s Alzheimer Research Offers Invaluable Insights On The Disease

Millions of people across the globe suffer from Alzheimer’s disease. It is estimated (Alzheimer’s Association, 2008) that in every 71 seconds someone from the US develops Alzheimer’s disease, and estimations by mid-century shows that the probability of someone developing Alzheimer’s disease is every 33 seconds. At present, there are approximately 5.2 million Americans in all age groups who suffer from Alzheimer’s disease; and 13% of these patients fall in the age category of 65 years and older. It is calculated that by 2050 the number of Alzheimer’s patients falling in the age category of 65 years and older will increase to a range of over 11 million to 16 million alone (Alzheimer’s Association, 2008). The facts and figures are alarming and bring our focus to the unmet demand for effective therapeutics and new researches for treatments related to Alzheimer’s disease.

Dr. Michael Mullan is an accredited professional from biomedical field. He has extensively researched on the causes and prospective cures of Alzheimer’s disease and other neurodegenerative disorders conditions. Based in Sarasota, Florida, he is reputed Director of Roskamp Institute. He is a highly qualified professional and has dedicated his time to finding cures for neuropsychiatric and neurodegenerative disorders and addictions. Dr. Mullan’s Alzheimer research work has provided invaluable insights on the disease with which many potential cures have been developed and tested. Dr. Mullan’s Alzheimer research indicates that one of the causes directly related to the disease is the excess accumulation of beta-amyloid, a type of protein, present in the brain. It was estimated that the protein is produced in every human but its excess accumulation can result in Alzheimer’s. Besides, Dr. Mullan’s Alzheimer research continuously tests medications and therapeutic treatments to help slow down the accumulation of beta-amyloid and related inflammation in patients.

About Dr Michael Mullan

Dr Michael Mullan has been working in the biomedical field for many years. He is a leading researcher with special expertise in assessment of the earliest cognitive symptoms and stages of Alzheimer’s disease. Mullan’s Alzheimer research works are also published in various articles which help students and researchers for making new discoveries. Find out more about his Alzheimer research works, by browsing through www.rfdn.org or www.mullanalzheimer.com or www.mullanalzheimer.info.

Dr. Mullan’s Alzheimer Research Identified Various Genetic Variations

Based in Sarasota, Florida, The Roskamp Institute is a not-for-profit organization. It has dedicated time to finding cures for several neuropsychiatric disorders with a special emphasis on Alzheimer’s disease (AD). In order to develop therapeutic targets which are specific to Alzheimer’s disease etiology, the scientists engaged in current research at Roskamp Institute focus on dissecting the molecular biological pathways which are associated in Alzheimer’s disease pathogenesis.

Dr. Michael Mullan is the Director of the Roskamp Institute, and along with his team, he discovered the concept of ‘Swedish mutation’, a genetic error which results in overproduction of beta-amyloid by aberrant proteolytic processing of amyloid precursor protein (APP).  The concept of Swedish mutation now forms the bases of most mouse model of Alzheimer’s disease. Many tests and findings by the Roskamp Institute resulted in several therapeutic prospects for the treatment of Alzheimer’s disease as well as Cancer.

The Roskamp Institute has contributed greatly by providing research on the treatments of several neuropsychiatric disorders like traumatic brain injury, substance abuse, and Alzheimer, etc. With the guidance and knowledge provided by Dr. Mullan, the institute tested many causes and correlations between Alzheimer’s disease and proteins present in human brain. With Dr. Mullan’s Alzheimer research, several types of genetic variations, which can be the cause of Alzheimer’s, have been identified. It was discovered that the central reason to the disease process is a small protein identified as the ß (beta)-amyloid. Although, this protein is present normally in the human brain, but at times excess or abnormal accumulation can result in Alzheimer’s disease. With Dr. Mullan’s Alzheimer research, the institute tests cutting edge cures, therapeutic treatments and medications to slow down the process of toxic ß-amyloid accumulation.

Dr Mullan’s Alzheimer research proves that Aβ peptide prevents blood vessel growth and eventually inhibits tumor growth in brain. To identify if Aβ has the same effect with short derivatives, he studied various sequences within the Alzheimer’s Aβ peptide which have potential therapeutic relevance in preventing tumor growth. Dr. Mullan’s Alzheimer research work has contributed exceptionally to the field to help understand the disease and find its cures. Find out more about his Alzheimer research works, by browsing through www.rfdn.org or www.mullanalzheimer.com or www.mullanalzheimer.info.

Family History of Alzheimer’s disease – what does it mean?

Frequently in the Roskamp institute Memory Clinic we are asked what a family history of Alzheimer’s disease means for the children and other blood relatives of sufferers.  Although this question is always handled on an individual basis there are some general guidelines that can be offered to access risk for the disease to children and other family members related to a sufferer.  Naturally, family members who perceive they are at risk for developing the disease themselves may suffer from a great degree of anxiety it is therefore important to ask the staff at the Roskamp Institute what the individual risk is for developing the disease.  In general the genetic risk for Alzheimer’s disease can be divided into two categories; early onset familial disease which is highly genetic and occurs in families which may have onsets of the disease in the 40s,50s or 60s;  late onset disease which is frequently familial but where the disease onsets in the seventh decade onwards.  We shall consider these two scenarios separately.

Early onset Alzheimer’s disease.

The term “early onset Alzheimer’s” is frequently misunderstood or used in a confusing way.  What we generally mean by  early onset Alzheimer’s is Alzheimer’s that onsets before the age to 60 years.  This is in contrast to the term early onset as referencing the early stage of the disease.  This is a confusing way to use the term and is discouraged.  Early stage disease is a better term to describe the early phases of the disease. Early onset familial disease occurs in families that are affected in multiple generations by mutations in genes that can trigger the disease.  Families of early onset disease thankfully are very rare but they have provided great insight into the disease process probably in all cases of the disease (early and late onset).  Sadly, frequently in these families the disease is inherited in what is known as an autosomal dominant fashion.  Autosomal dominant inheritance means that 50% of the offspring of each generation on average are impacted by the disease.  Some generations may be very fortunate and although they may be at risk for inheriting the diseased gene from one or the other parent none of the siblings in a sibship may be affected.  On the contrary sibships can be very unlucky in which case more than 50% are impacted with the disease.  For each child of an affected parent there is a 50% chance of inheriting the disease and this chance is not influenced by whether other siblings have already inherited the disease or not.

Unfortunately the inheritance of these rare genetic variance means that individuals at risk are highly likely to develop the disease if they live long enough.  One of the important characteristics of these familial mutations is that the disease tends to onset around approximately the same time of life.  Thus if a family has a mean (average) age of onset of 52 and one inherits one of these rare generic  errors then one is unlikely to live to 60 without developing  signs or symptoms of the disease.  By contrast if one does not carry the mutation then there is no more risk for the disease than the general population.

Again it is most important to emphasize that such families are extremely rare and early onset Alzheimer’s is not the most likely reason for patients or their families to visit the Roskamp Institute Clinic.  In fact, approximately 1% or less of cases of Alzheimer’s Disease have what can be described as early onset disease.  In the past, individuals who come from such families have sought genetic counseling including genetic testing for these genetic errors.  It is relatively straightforward to detect such errors but clearly the genetic information is highly sensitive.  Family members should therefore think very carefully before seeking such information however initially finding out more about early onset disease is a recommended step.

Clinicians at the Roskamp Institute are happy to discuss early onset disease with patients and their families as they wish.  Finally it should be noted that many cases of early onset disease occur without a family history.  Thus individuals can manifest the disease before the age of 60 but have no other known family members either in the prior generations or in subsequent generations that develop the disease the cause of early onset Alzheimer’s that is not familial is not well understood but importantly there is no risk to subsequent family members for development of the disease.

Late onset (common) Alzheimer’s disease.  Much more commonly patients and their families come to the clinic at the Roskamp Institute and seek advice on the inheritance of Alzheimer’s when one or more members of the family has late onset disease.  This is defined as disease which onsets over the age of 60 and this is by far in a way the most common cause of the disease. It is estimated that approximately 4 million Americans presently either have the disease or are in the early or pre clinical stages – most of these cases are late onset Alzheimer’s Disease.  The predicted numbers for future disease prevalence are very high. For instance it is estimated that by mid century there could be as many as two hundred million individuals afflicted with the disease.

Most late onset Alzheimer’s disease does not exhibit a clear autosomal dominant pattern meaning that the risk to offspring of individuals suffering with the disease is usually considerably less than 50%.  Certain genetic risk factors for late onset disease have been identified – the most important of which is apolipoprotein E (APOE).  There are 3 common forms of APOE: E2, E3 and E4.  The discovery by Allen Roses and his colleagues at Duke University showed that Alzheimer’s disease sufferers were much more likely to carry one or two copies of the E4 allele (genetic form) of APOE than the normal population.  Carrying one copy of APOE 4 increases ones risk for the disease by approximately three times and carrying two copies can increase the risk for the disease by up to fifteen times compared to individuals who do not carry an APOE 4 allele.

Many family members express interest in being genetically tested for their risk for the disease.  Such tests are commercially available but most centers discourage the use of testing prior to symptoms because many individuals who carry an APOE 4 allele do not necessarily develop the disease at least until late old age.  Conversely it’s very possible to develop Alzheimer’s disease without carrying an APOE 4 allele. Therefore on an individual basis the test is not overly helpful in specifying who may or may not develop the disease.  However on a group basis APOE genetic testing is very helpful to give an average estimate of the numbers of individuals who will subsequently develop Alzheimer’s.

It is anticipated that as better treatments are available for Alzheimer’s disease there will be greater interest in genetic testing.  For instance it is expected that as treatments are used earlier and earlier in the stages of the disease that individuals in the very early stage or maybe with no symptoms at all might seek medical treatment once such treatment has been established as effective in stopping the rate of progression or disease onset.

Despite the fact that genetic testing is not used frequently in clinical practice it is a tremendous tool in assisting researchers in understanding when and why the diseases develops and in planning clinical trials to take into account who is most likely to develop the disease.  Already there is evidence from several clinical trials that individuals that carry the APOE 4 allele may be more refractory to certain treatments.  As drug development progresses it will be important to develop medications that are able to tackle the severest form of the disease i.e. those patients who are carrying and APOE 4 allele.

Summary:   The two types of familial Alzheimer’s disease differ in the risk for offspring of developing the disease.  The early onset cases as noted have children that are highly at risk for developing the disease if there is a family history.  By contrast late onset disease or low clustering in families is much less genetically predisposed.  In both cases genetic tests are available but are generally discouraged particularly for late onset disease.  Roskamp Institute researchers and clinicians are well versed in the genetic aspects of the disease and can advise on an individual or family basis as required.

The Roskamp Institute is a not-for-profit research Institute located in Sarasota and Tampa, Florida, that is dedicated to understanding the causes of, and finding cures for, neuropsychiatric and neurodegenerative disorders and addictions with an emphasis on Alzheimer’s disease. The Institute’s Memory Clinics also offer comprehensive cognitive and medical assessment toward differential diagnosis of Alzheimer’s disease and offers treatments and disease management options once the diagnostic evaluation is complete.

By Dr. Michael Mullan, Director of Alzheimer Research Institute, The Roskamp Institute

for more information on Alzheimer’s please visit:

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Why work with Alzheimer’s disease patients?

Walking into the Memory Disorder Clinic at the Roskamp Institute one might ask “Why work with Alzheimer’s patients and their families?”  The answers are manyfold.  One of the most rewarding aspects of working with Alzheimer’s patients is that they are most commonly our oldest citizens who have 60, 70 or 80 years of life experience behind them  many of them have served their country in one form or another  - frequently in the military but often times in businesses working for others or their own companies.  Many of those serving in the armed forces have captivating stories.  One visitor to the clinic had parachuted into three war zones Normandy, the “boot” of Italy, and Germany.  Remembering this tale this gentleman was most afraid of being shot by the Russians!  Of course being able to recall these old memories is not unusual for Alzheimer disease suffers.  In fact the tendency to reminisce sometimes becomes a prominent feature of the disorder.  Most caregivers are initially concerned by another aspect of the disorder namely the forgetfulness for recently acquired or presented information.  Such things as recent visits recent phone calls or recent conversations and events may not be remembered either in part or in full.  This distressing symptom interferes with social activities and is a progressive aspect of the disease.  Therefore one of the most rewarding aspect of working with Alzheimer’s sufferers and their families is being able to convey to them the several treatment options that are available.  This includes, as well as those drugs approved by the FDA, new and experimental treatments including those that are being developed by the Roskamp Institute itself.  

Providing hope for patients and their families is a critical part of interfacing with them.  In addition helping families to come to terms with a disorder  that can impact many aspects of  their love ones’ lives (including social interactions, pastimes and sports, financial transactions and medical legal issues) enables families to make the necessary adjustments  to deal with the condition.  Naturally a particularly satisfying interaction can occur when certain elements of a patient’s health can be altered to improve the outcome once a diagnosis of Alzheimer’s has been made.  For instance we know that cardio-vascular health interacts critically with Alzheimer’s disease and aversion of cerebrovascular events (such as small strokes or transient ischemic attacks) has a highly beneficial effect on the outcome of Alzheimer’s patients.  In addition other conditions such as diabetes or thyroid disease can interact negatively with the disease.  These and many other treatable causes of cognitive dysfunction appear at the Roskamp Memory Clinic and are regularly amenable to intervention.  Sometimes previous diagnoses are found to be incorrect and memory loss may be completely reversible.  For instance people suffering from normal pressure hydrocephalus have a condition that is completely amenable to surgical correction.

Another gratifying aspect of working with Alzheimer’s patients is being able to give their families and loved ones a clear indication of what the treatment options are and what the outcomes are likely to be.  In addition family members are often concerned about their own risk for developing the disease it now being common knowledge that the disease has a familial aspect.

All in all there is much to recommend a profession working and caring for Alzheimer’s patients. Our elderly are frequently amongst our most valued citizens who have contributed to the prosperity and safety of subsequent generations.  Continuing to work for their immediate care and finding new treatments to improve their long term prognosis are the premier interests of the Roskamp Institute’s researchers, physicians and clinicians.

Alzheimer’s disease drug developed at Roskamp Institute approved for key clinical trial funding in Europe

Nilvadipine, an Alzheimer’s drug developed at the Roskamp Institute in Sarasota announced earlier this year was selected for funding or a large-scale European clinical trial. An international research consortium led by Trinity College Dublin (Ireland) announced more than 500 patients will participate in the multicenter Phase III clinical trial designed to study the effectiveness of Nilvadipine.

Michael Mullan, M.D., Ph.D., Roskamp Institute director who, with associate director Fiona Crawford, Ph.D and lead scientist Daniel Paris, Ph.D., led the research team that developed the drug. Mullan said, “We need many more medicines to move forward into advanced clinical trials in the fight against Alzheimer’s Disease and we are pleased the Roskamp institute has played such a major role in the development of this drug.” Before a drug can move into clinical practice, Phase III is usually the last step in the regulatory process.

The clinical trials will take place in Europe, where Brian Lawlor, M.D., Connolly Norman Professor of Old Age Psychiatry at Trinity College Dublin, Ireland, will be principal investigator and coordinator. The study will be funded by the European Commission Seventh Framework Programme and more than 20 European clinical sites will participate. Nilvadipine is already approved for the use in mild cases of hypertension (high blood pressure) and Mullan says, “The process can move more quickly in Europe, and the study findings may help accelerate the process with the U.S food and Drug Administration (FDA).

Mullan and Crawford have been studying Alzheimer’s disease for more than 20 years, moving from the UK to Florida in 1991 and to Sarasota in 2003 to establish the Roskamp Institute. “Some of our recent studies have involved Sarasota area residents, who have contributed to our understanding of Alzheimer’s disease and helped move the development process forward,” said Crawford. Now, the Roskamp Institute will provide research support for the Phase III clinical trial, such as assessing genetic and other markers for Alzheimer’s disease in study participants.

For more information on Alzheimer’s Disease please visit www.mullanalzheimer.com

Or http://mullanalzheimer.info

Or www.rfdn.org

Roskamp institute studies may lead to better diagnosis

Researchers at the Roskamp Institute have new studies that could lead to better diagnosis and eventual treatment for U.S. military personnel as well as other patients with TBI, commonly known as traumatic brain injuries.

Fiona Crawford, Ph.D., associate director of the Institute, a leading research facility for Alzheimer’s disease and other neurological disorders says, “We have found that there are changes in blood proteins that occur after a head injury, and that these are dependent on the severity of the injury, the time since the injury and genetic factors influencing outcomes after head injury.” Crawford’s research indicates that TBI can affect cellular mechanisms in the brain long after the original trauma, and that blood biomarkers reflect these ongoing processes. She also stated, “Translating these finding from the laboratory to human patients may help clinicians determine the extent of the brain injury, how long ago the injury occurred and the patient’s prognosis for a favorable or a poor outcome.”

Traumatic brain injury has multiple consequences at the cellular level and so molecular changes can persist for weeks and months after the initial brain swelling and other immediate issues have resolved. Crawford says, “Identifying blood biomarkers of mild TBI would improve medical management by enabling us to identify patients who need treatment or intervention, even if they do not have obvious signs of a brain injury.” The U.S. Department of Defense, and the Veterans Administration supports all of Crawford’s work because it could lead to better diagnosis of military personnel with mild brain injuries and better long-term care of our veterans.

For more information on Alzheimer’s Disease please visit www.mullanalzheimer.com

Or http://mullanalzheimer.info

Or www.rfdn.org

Research Highlights The Direct Causes Related To The Disease

Alzheimer’s disease affects patients over 65 years of age and is classified as a type of dementia. However, the less prevalent early-onset Alzheimer’s can also occur earlier than 65 years of age as shown by several researches. As per the 2006 statistics, there were 26.6 million patients of Alzheimer’s and it is estimated that the disease will affect 1 in 85 people globally by 2050. Presently, there are no cures available for the disease and it is estimated to get worse with age gradually leading to death. Alzheimer’s is calculated to affect a person’s memory, affects the ability to learn and also types of behavioral changes.
Dr. Michael Mullan is a highly accredited biomedical professional and has contributed vastly to the field of research on neurodegenerative disorders conditions such as Alzheimer’s disease. He is chaired as the Director at Roskamp Institute. He is based in Sarasota, Florida, and is exceptionally qualified in finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Roskamp Institute utilizes superior scientific approaches along with Dr. Mullan to understand the root causes and potential therapies of disorders such as Alzheimer’s disease. Aside researching on Alzheimer’s, the institute has successfully studied other illnesses and disorders such as Gulf War Illness, Brain Research, etc.
With Dr. Mullan’s Alzheimer research, science has come to a better understanding of the disease and of developing its prospective cures. Dr. Mullan’s Alzheimer research proves that one of the direct causes related to the disease is the excess accumulation of beta-amyloid which is a type of protein in the brain. It is noticed that the protein is produced in every human, but its excess accumulation can result in Alzheimer’s. Along with the team, Dr. Mullan’s Alzheimer research has tested many medications and therapeutic treatments to help slowing down the accumulation of beta-amyloid and associated inflammation.
About Dr Michael Mullan
Dr Michael Mullan has been working in the biomedical field for many years. He is a leading researcher with special expertise in assessment of the earliest cognitive symptoms and stages of Alzheimer’s disease. Mullan’s Alzheimer research works are also published in various articles which help students and researchers for making new discoveries. Find out more about his Alzheimer research works, by browsing through www.rfdn.org or www.mullanalzheimer.com or www.mullanalzheimer.info.

Dr. Mullan’s Alzheimer Research Involved Studying Brain Proteins

The Roskamp Institute has surfaced as a leading and reputable non-for-profit biomedical research organization. It has successfully experimented to find cures for several neurodegenerative disorders and conditions like Alzheimer’s disease. Through the clinical trials division and outpatient clinic, at the institute, thousands of Alzheimer’s patients get superior services and therapeutic treatments. Dr. Michael Mullan is the Director of Roskamp Institute. Dr. Mullan is an experienced and a competent individual. His research efforts led to the identification of Swiss Mutation.
Along with Dr. Mullan, the institute has helped in contributing to provide insights on the treatments of neuropsychiatric disorders such as Alzheimer, traumatic brain injury, substance abuse, etc. through unparalleled research. Under the supervision and guidance of Dr. Michael Mullan, several causes and cures related to Alzheimer’s disease have been found. Dr. Mullan’s Alzheimer research identified various types of genetic variations which may be the cause of predispose humans to this disease. His research and study identified that the central reason to the disease process is a small protein known as ß (beta)-amyloid. The excess and abnormal accumulation of ß-amyloid in the brain results in Alzheimer’s disease. With Dr. Mullan’s Alzheimer research, cutting edge cures, medications, and therapeutic treatments are tested and developed to help slow down the process of ß-amyloid’s toxic accumulation.
As per the research on Dr Mullan’s Alzheimer, Aβ peptide is responsible for preventing blood vessel growth and inhibiting tumor growth. He studied several particular sequences within the Alzheimer’s Aβ peptide to identify if Aβ can have the same effect with short derivatives as well. The research proved that the peptide has potential therapeutic relevance to prevent the growth of tumor. The research involved conducting clinical trials which are specifically conducted to developing superior treatments for neurodegenerative diseases. In order to understand the diseases and finding its causes and prevention, Dr. Mullan’s Alzheimer research work has contributed extraordinarily in the field. Furthermore, with his constant efforts and guidance, the Roskamp Institute was also able to carry out research in neuropsychiatric disorders such as Traumatic Brain Research, Gulf War Illness, and Alzheimer’s. Find out more about his Alzheimer research works, by browsing through www.rfdn.org or www.mullanalzheimer.com or www.mullanalzheimer.info.

Roskamp Institute researchers show that some antibodies but, not others may be helpful in removing the Alzheimer amyloid from the brain of Alzheimer’s sufferers.

The Roskamp Institute researchers show that some antibodies but, not others may be helpful in removing the Alzheimer amyloid from the brain of Alzheimer’s sufferers. Drs. Corbin Bachmeier, Daniel Paris, and Michael Mullan at the Roskamp Institute have been working on ways to improve the removal of the Alzheimer amyloid peptide from the brain. Using antibodies to amyloid and in an vitro model of the blood brain barrier, the Roskamp Institute researchers have shown that certain antibodies can enhance the clearance of amyloid from the brain side to the blood side. However, they also showed that other antibodies were not able to do this. The researchers explained that the difference in ability to remove amyloid has to do with a receptor called RAGE. The RAGE receptor is responsible for taking amyloid from the blood into the brain. The researchers suggested that the antibodies which bind amyloid but block its uptake by RAGE keep amyloid in the blood and thus, allow its removal from the body by the liver. As a consequence of removal of amyloid from the blood, more amyloid flows from the brain into the blood. However, antibodies which bind amyloid but still allow it to be taken up by the RAGE receptor do not stop it from being taken back from the blood into the brain. Thus, antibodies which bind amyloid and block its uptake by the RAGE receptor are thought to be most preferable. Antibodies to the Alzhemier amyloid peptide are being developed by a number of pharmaceutical companies to encourage the removal of amyloid from the Alzheimer brain.

The Roskamp Institute, under the leadership of Drs. Michael Mullan and Fiona Crawford, is dedicated to finding new treatments and cures for Alzheimer’s disease and related disorders.

Microcirculation. 2011 Jul;18(5):373-9. Epitope-dependent effects of Beta-amyloid antibodies on Beta-amyloid clearance in an in vitro model of the blood-brain barrier. Bachmeier CJ, Beaulieu-Abdelahad D, Mullan M, Paris D.

 

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<a href=’http://www.mullanalzheimer.info’>http://www.mullanalzheimer.info</a>

michael mullan, alzheimer, mullan alzheimer, mullan roskamp, roskamp institute, amyloid

Mullan Alzheimer Research Institute Roskamp Institute aids high school students in genetic research

Dr. Mullan Alzheimer Research Institute helps high school student to be involved in research………

Roskamp Institute aids high school students in genetic research

Roskamp aids high school students in genetic research

By JENNIFER RICH – jrich@bradenton.com

They look like scientists in their white coats, working in the Roskamp Institute’s lab using microscopes and high-tech research equipment.

But they’re high school students doing genetic research just like the adults working alongside.

It’s probably the best hands-on learning experience in the world for teens who hope to major in fields like chemical engineering and organic chemistry when they go to college, says James Humphrey, chief operating officer at Roskamp.

Read more: http://www.bradenton.com/2011/11/14/3649043/bridging-the-gap.html#ixzz1dgyk7Niz

 

 

The Roskamp Institute investigates the role of anatabine in lowering Alzheimer’s Abeta levels.

The Roskamp Institute has had a long-term interest in finding new treatments for Alzheimer’s disease. Central to the goal of the institute is finding new ways to lower the accumulation of Alzheimers Abeta peptide in the brain. Drs. Michael Mullan and Daniel Paris and colleague investigated the role of an extract of tobacco, known as anatabine in the production and accumulation of the Alzheimer Abeta peptide. Paris and Mullan and colleagues showed that anatabine did lower the production of the Alzheimers Abeta peptide in cell culture — in cells genetically engineered to produce the Alzheimers Abeta peptide. In addition, they showed that al  in an animal model of Alzheimer’s disease which overproduces the Alzheimers  Abeta peptide, anatabine was able to lower the accumulation of amyloid in the brain. The paper cited below that resulted from this work was published in the European Journal of Pharmacology in September of 2011. Collectively, the work suggests that anatabine, a naturally occurring tobacco product and one which occurs in other plants and is in the human food chain, may have potential beneficial effects in Alzheimer’s disease.

The Roskamp Institute, headed by Drs. Michael Mullan and Fiona Crawford is dedicated to finding new treatments for Alzheimer’s disease. Drs. Mullan and Crawford were among those who first showed that certain early onset forms of Alzheimer’s are caused by accumulation of Alzheimers Abeta peptide. These findings contributed to the worldwide use of models of Alzheimer’s disease which contain human mutant amyloid precursor protein.

Eur J Pharmacol. 2011 Sep 19. [Epub ahead of print] Anatabine lowers Alzheimer’s Aβ production in vitro and in vivo.
Paris D, Beaulieu-Abdelahad D, Bachmeier C, Reed J, Ait-Ghezala G, Bishop A, Chao J, Mathura V, Crawford F, Mullan M.

 

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Dr. Mullan Alzheimer Presentation at Pines of Sarasota

Alzheimer’s disease: Amyloid Plaque (Excerpt from “On The Forefront”)  Video shows Dr. Michael Mullan (Dr. Mullan Alzheimer Researcher at the Roskamp Institute) presenting information to audience about Alzheimer’s Disease.Beta Amyloid Presentation By Dr. Michael Mullan (Mullan Alzheimer Researcher)

Roskamp Institute Celebrated Veterans Day with a seminar by Alzheimer Researcher Dr. Michael Mullan

Dr. Fiona Crawford presentedVideo of Alzheimer Research Institute Headed By Dr. Mullan Presentation on Traumatic Brain Injury a synopsis
of her recent study of traumatic brain injury
(TBI). Her recently published findings
show how TBI can affect the brain’s
inflammatory mechanisms, changes in
protein levels and cellular pathways, long
after the original trauma. Dr. Crawford’s
work has been followed closely by the
U.S. Department of Defense, because it
could lead to better diagnosis of military
personnel with mild brain injuries.

 

 

 

 

Dr. Fiona Crawford — Discussion of research programs underway at
Roskamp Institute with Veterans and current combat military personnel
Dr. Michael Mullan – Research and treatment being done in
Alzheimer’s Disease, dementia, depression, and related disorders
Dr. Andrew Keegan – Associate Director, Roskamp Institute Clinic
Memory screens, clinical trials, neurological services
Tours available of Roskamp Institute Research Laboratory
Veteran’s Administration representatives will be on site
Information tables and Roskamp Institute personnel to discuss clinic services,
memory screens, clinical drug trials and volunteer opportunities.

Dr. Mullan’s Alzheimer Research Notes on NSAIDS and their effect on Alzheimers disease

Non-steroidal anti-inflammatory (NSAIDS) drugs such as Naproxen and Celecoxib do not improve cognition in at-risk older adults. These findings from the Alzheimer’s Disease Anti-Inflammatory Prevention Trial (ADAPT) were published this month in Archives of Neurology. The Roskamp Institute Memory Clinic in Tampa was one of a handful of centers across the United States that took part in this primary prevention trial funded by the National Institute of Aging. The Tampa site enrolled over 400 subjects, age 70 or older with a reported family history of Alzheimer’s-like dementia. During the 5-year study period, participants underwent annual cognitive testing and were randomly assigned to one of two treatments (Naproxen 220 mg twice daily, Celecoxib 220 mg twice daily) or a placebo. Although treatment was suspended in 2004, following a report of increased cardiovascular risk in another prevention trial, subjects continued annual follow-up. Results examining the cognitive data collected up to 6 months after treatment was discontinued suggest that Naproxen may in fact have a small deleterious effect on cognition. However further study is needed to determine if this effect is mitigated or exaggerated over time, or if results were influenced by subjects who may have been in the early stage of a dementia. Drs. Cheryl Luis and Timothy Crowell, specialists in Neuropsychology, supervised the day-to-day aspects of the study in Tampa. Dr. Michael Mullan, director of the Roskamp Institute and principal investigator for the Tampa site served on the writing committee of the manuscript. Go to http://www.ncbi.nlm.nih.gov/pubmed/18474729 for more information. Also please read other interesting articles at the Dr. Mullan’s Alzheimer Research notes website: http://www.mullanalzheimer.com