Alzheimer’s disease is the most common type of dementia in the elderly. Alzheimer’s Disease is mainly characterized by the accumulation of a small molecule (known as amyloid beta (Abeta) in the brain. Many researchers have shown that the molecule CD40L is elevated in Alzheimer’s Disease patients. Roskamp Institute research group headed by Dr. Michael Mullan also have shown that CD40L stimulation increases Abeta levels in cellular models of the disease. Furthermore, we have 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 Alzheimer’s Disease with increases in pro-inflammatory cytokines. In the cytokine paper, we have shown that CD40L stimulation increases the levels of both GM-CSF and Abeta in Alzheimer’s Disease cell models. We have shown that treatment of these cells with GM-CSF causes a time dependent significant increase in Abeta levels. We demonstrate that blocking GM-CSF reduces CD40L-induced Abeta production in a dose dependent manner. In addition, we show that inhibiting GM-CSF signaling by silencing the GM-CSF receptor gene significantly reduces Abeta levels to below basal levels in non-CD40L-stimulated by blocking the trafficking of Abeta’s mother protein, the amyloid precursor protein. Our results that are now published in the Journal cytokine (Volmar et al., 2008) suggest that GM-CSF operates downstream of CD40/CD40L interaction and that GM-CSF modulates Abeta production. The Roskamp Institute specializes in Alzheimer’s Disease research and under the leadership of Dr Michael Mullan has focussed on the role of inflammation in Alzheimer’s Disease and on new treatments for Alzheimer’s Disease and other disorders. Mullan and colleagues have been examining ways to treat Alzheimer’s Disease by inhibiting the CD40 pathway.
The granulocyte macrophage colony stimulating factor (GM-CSF) regulates amyloid beta production (2008). Volmar CH, Ait-Ghezala G, Frieling J; Paris D, Mullan MJ Cytokine 42(3):336-44.
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