Microglial Scavenger Receptors and Their Roles in the Pathogenesis of Alzheimer's Disease

Alzheimer's disease (AD) is increasing in prevalence with the aging population. Deposition of amyloid- β (A β ) 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 β appears to play a dichotomous role in AD pathogenesis. On one hand, microglia can phagocytose and clear A β , but binding of microglia to A β 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 β . 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 β , while CD36 and RAGE are involved in activation of microglia by A β . In this review, we discuss the roles of various scavenger receptors in the interaction of microglia with A β 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.