Microglia, scavenger receptors, and the pathogenesis of Alzheimer's disease.
The senile plaque is the pathological hallmark of Alzheimer's disease. Senile plaques are composed of beta amyloid fibrils, associated with activated microglia, astrocytes, and dystrophic neurons. We have recently identified class A scavenger receptors as the main receptors mediating the interaction of microglia with beta amyloid fibrils. Adhesion of microglia to beta amyloid fibrils leads to immobilization of these cells on the fibrils, and induces them to produce reactive oxygen species. We propose that interactions of microglial scavenger receptors with fibrillar beta amyloid may stimulate the microglia to secrete apolipoprotein E and complement proteins, which may further contribute to neurotoxicity and neuronal degeneration. Therefore, microglial scavenger receptors may be novel targets for therapeutic interventions in Alzheimer's disease.
El Khoury
J
J
Department of Medicine, Beth Israel Medical Center, Albert Einstein College of Medicine, New York, NY, USA. jbe1@columbia.edu
Hickman
S E
SE
Thomas
C A
CA
Loike
J D
JD
Silverstein
S C
SC
D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D016166:Free Radical Scavengers / Q000378:metabolism*; D006801:Humans; D017628:Microglia / Q000378:metabolism*; D017382:Reactive Oxygen Species
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species