Mechanism of Microglial Recruitment in AD

Joseph El Khoury, MD Massachusetts General Hospital

Project Details

Data from humans with Alzheimer's disease and animal models of the disease indicate that the accumulation of microglia (inflammatory cells) in senile plaques contributes significantly to neural degeneration. Previous research from both Dr. El Khoury's laboratory and from other scientists indicates that beta-amyloid activates local microglia and astrocytes to produce chemokines, which then attract additional microglia to the plaque. The recruited microglia bind to the already deposited beta-amyloid and become activated to produce neurotoxins and other inflammatory mediators that cause neuronal damage. With prior support from ADR, Dr. El Khoury found that a small protein, called MCP-1, is necessary for the recruitment of microglia to sites of beta-amyloid deposition, and he has hypothesized that this protein may play a role in the recruitment of microglia to senile plaques in Alzheimer's disease. He is now working to build upon this data by investigating the specific mechanisms of recruitment, activation, and retention of microglia in senile plaques.