Alzheimer disease is the most common cause of dementia, afflicting 24 million people worldwide. Over time, Alzheimer's disease gradually destroys a person's memory and ability to learn and carry out daily activities. In addition; individuals may also experience changes in personality and behavior. Alzheimer disease is accompanied by the presence of amyloid plaques and neurofibrillary tangles in the brain of Alzheimer's patients with increases in pro-inflammatory cytokines. Beta-amyloid (Alzheimer’s Aβ) is a key protein shown to play a central role in Alzheimer's disease etiology. Unfortunately, there is currently no known cure, finding a way to stop Alzheimer’s Aβ production and/or increase it degradation will lead to a potentially drug target that can be used to stop the disease. The granulocyte macrophage colony stimulating factor (GM-CSF) is a signaling protein used extensively in cellular communication. GM-CSF has been suggested to induce programmed cell death in the brain tissue of patients with Alzheimer’s Disease. Scientist at the Roskamp institute showed that blocking this protein reduce the production of the main pathological protein that causes Alzheimer's disease (Alzheimer’s Aβ ) below basal level. In addition the Roskamp Institute scientists examined the mechanism underlying Alzheimer’s Aβ reduction after silencing of the receptor protein of G-CSF. Their result show that these effect is due to the fact that blocking the GM-CSF receptor reduce APP (Beta-amyloid protein precursor) trafficking from the cell membrane to the inside of the cell were the preotein in cleaved to generate the Alzheimer’s Aβ fragment. The discovery is detailed in an article appears in the journal Cytokine. 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 previously published papers showing that inflammatory molecules like CD40 adversely contribute to Alzheimer’s Disease that that blocking CD40 signaling could help prevent the pathology that occurs in Alzheimer’s Disease.
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.
Microglial activation resulting from CD40-CD40L interaction after beta-amyloid stimulation (1999). Tan J, Town T, Paris D, Mori T, Suo Z, Crawford F, Mattson MP, Flavell RA, Mullan M. Science, 286(5448):2352-5.
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