Microglial Aβ Receptors in Alzheimer's Disease

Amyloid beta (A beta) plays a pivotal role in the progression of Alzheimer's disease (AD) through its neurotoxic and inflammatory effects. On one hand, A beta binds to microglia and activates them to produce inflammatory mediators. On the other hand, A beta is cleared by microglia through receptor-mediated phagocytosis and degradation. This review focuses on microglial membrane receptors that bind A beta and contribute to microglial activation and/or A beta phagocytosis and clearance. These receptors can be categorized into several groups. The scavenger receptors (SRs) include scavenger receptor A-1 (SCARA-1), MARCO, scavenger receptor B-1 (SCARB-1), CD36 and the receptor for advanced glycation end product (RAGE). The G protein-coupled receptors (GPCRs) are formyl peptide receptor 2 (FPR2) and chemokine-like receptor 1 (CMKLR1). There are also toll-like receptors (TLRs) including TLR2, TLR4, and the co-receptor CD14. Functionally, SCARA-1 and CMKLR1 are involved in the uptake of A beta, and RAGE is responsible for the activation of microglia and production of proinflammatory mediators following A beta binding. CD36, CD36/CD47/alpha 6 beta 1-intergrin, CD14/TLR2/TLR4, and FPR2 display both functions. Additionally, MARCO and SCARB-1 also exhibit the ability to bind A beta and may be involved in the progression of AD. Here, we focus on the expression and distribution of these receptors in microglia and their roles in microglia interaction with A beta. Finally, we discuss the potential therapeutic value of these receptors in AD.