Alzheimer Expert Dr. Mullan’s comments on CD40L induces Abeta production via signaling by the granulocyte macrophage colony stimulating factor (GM-CSF)

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Abeta Amyloid Mullan Alzheimer

Abeta Amyloid Mullan AlzheimerAlzheimer’s disease (AD) is the most common type of dementia in the elderly. AD is mainly characterized by the accumulation of a small molecule (known as amyloid beta (Ab)) in the brain. Many researchers have shown that the molecule CD40L is elevated in AD patients. Roskamp Institute Alzheimer’s research group headed by Dr. Michael Mullan also have recently shown that CD40L stimulation increases Ab levels in cellular models of the disease. Furthermore, Mullan’s Alzheimer group has shown that CD40L stimulation of cells that are important for the defense of the nervous system induces increases in pro-inflammatory molecules known as cytokines. The granulocyte macrophage colony stimulating factor (GM-CSF) is one of these cytokines involved in inflammation responses in the brain. Numerous studies have correlated AD with increases in pro-inflammatory cytokines. In the cytokine paper, we have shown that CD40L stimulation increases the levels of both GM-CSF and Ab in AD cell models. We have shown that treatment of these cells with GM-CSF causes a time dependent significant increase in Ab levels. We demonstrate that blocking GM-CSF reduces CD40L-induced Ab production in a dose dependent manner. In addition, we show that inhibiting GM-CSF signaling by silencing the GM-CSF receptor gene significantly reduces Ab levels to below basal levels in non-CD40L-stimulated by blocking the trafficking of Ab’s mother protein, the amyloid precursor protein. Our results that are now published in the Journal cytokine (Volmar et al., in press) suggest that GM-CSF operates downstream of CD40/CD40L interaction and that GM-CSF modulates Ab production.

 

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