Microglial scavenger receptors and their roles in the pathogenesis of Alzheimer's disease

Abstract

Alzheimer's disease (AD) is increasing in prevalence with the aging population. Deposition of amyloid- (A) in the brain of AD patients is a hallmark of the disease and is associated with increased microglial numbers and activation state. The interaction of microglia with A appears to play a dichotomous role in AD pathogenesis. On one hand, microglia can phagocytose and clear A, but binding of microglia to A also increases their ability to produce inflammatory cytokines, chemokines, and neurotoxic reactive oxygen species (ROS). Scavenger receptors, a group of evolutionally conserved proteins expressed on the surface of microglia act as receptors for A. Of particular interest are SCARA-1 (scavenger receptor A-1), CD36, and RAGE (receptor for advanced glycation end products). SCARA-1 appears to be involved in the clearance of A, while CD36 and RAGE are involved in activation of microglia by A. In this review, we discuss the roles of various scavenger receptors in the interaction of microglia with A and propose that these receptors play complementary, nonredundant functions in the development of AD pathology. We also discuss potential therapeutic applications for these receptors in AD. © Copyright 2012 Kim Wilkinson and Joseph El Khoury.