High serum Abeta and vascular risk factors in first-degree relatives of Alzheimer’s disease patients

Share this postShare on Google+Share on LinkedInShare on FacebookTweet about this on TwitterEmail this to someone

Alzheimer’s disease is clinically characterized by progressive cognitive decline accompanied by the presence of amyloid plaques and neurofibrillary tangles in the brain of Alzheimer’s patients. A small protein fragment beta-amyloid (Abeta) with 42 amino acids is shown to deposit earlier in the disease process than the slightly shorter form (40 amino acid fragment).  Both species of this protein fragment are considered toxic to the brain and are shown to have an important role in causing Alzheimer’s disease.  Current research suggests that the disease process in Alzheimer’s begins long before the presence of palpable symptoms and widespread damage in the brain. Therefore, use of beta-amyloid seems promising in identification of individuals at-risk of developing Alzheimer’s disease.  Clinical studies have previously shown that blood and cerebrospinal fluid levels of Abeta may be helpful in diagnosis of Alzheimer’s disease but are influenced by factors such as presence of family history and other risk factors. The main objective of a recent study published by the scientists at the Roskamp Institute was to determine whether elevated blood Abeta levels among the first-degree relatives of patients with Alzheimer’s disease are associated with certain risk factors of cardiovascular disease that are also risk factors Alzheimer’s disease, such as hypertension.  Blood Abeta was measured in disease-free first-degree relatives of patients with Alzheimer-like dementia. Study participants were recruited as part of an ancillary study of the Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT subpopulation) which was funded by the National Institutes of Health (UO1AG15477).  Examination of Abeta in this group of individuals showed that Abeta(1-40) fragment was positively associated with age and use of anti-hypertensive medications, but a negative relationship was observed in those individuals who experienced some increase in systolic blood pressure, despite being on anti-hypertensive medication.  On the other hand, the more toxic Abeta(1-42) was associated with statin use (medications used for lowering cholesterol) and with high-density lipoproteins was observed among statin nonusers. These findings suggest that high Abeta in blood samples of family history-enriched individuals may be due to enrichment of vascular risk factors and may reflect presymptomatic stage of Alzheimer’s disease.  As anti-hypertensive medications and statins are considered to be protective against Alzheimer’s disease onset, it remains to be determined whether their association with Abeta reflects mitigation of Abeta-related toxicity in the brain. Longitudinal evaluation of blood Abeta in this cohort will provide a better understanding of the significance of this association in Alzheimer’s disease etiology.

By Abdullah L, Luis C, Paris D, Ait-ghezala G, Mouzon B, Allen E, Parrish J, Mullan MA, Ferguson S, Wood M, Crawford F, Mullan M. These findings were published in Molecular Medicine 2009 Mar-Apr;15(3-4):95-100.

The Roskamp Institute is devoted to understanding causes and finding cures for neuropsychiatric and neurodegenerative disorders and addictions. The Institute utilizes a broad range of scientific approaches to understanding the causes of and potential therapies for these disorders with an emphasis on Alzheimer’s disease. For more information, please call (941)752-2949