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Microglial Aβ Receptors in Alzheimer’s Disease

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Abstract

Amyloid β (Aβ) plays a pivotal role in the progression of Alzheimer’s disease (AD) through its neurotoxic and inflammatory effects. On one hand, Aβ binds to microglia and activates them to produce inflammatory mediators. On the other hand, Aβ is cleared by microglia through receptor-mediated phagocytosis and degradation. This review focuses on microglial membrane receptors that bind Aβ and contribute to microglial activation and/or Aβ 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 Aβ, and RAGE is responsible for the activation of microglia and production of proinflammatory mediators following Aβ binding. CD36, CD36/CD47/α6β1-intergrin, CD14/TLR2/TLR4, and FPR2 display both functions. Additionally, MARCO and SCARB-1 also exhibit the ability to bind Aβ 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 Aβ. Finally, we discuss the potential therapeutic value of these receptors in AD.

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Acknowledgments

This work was supported by grants from National Natural Science Foundation of China (Grant 31270941 to R.D.Y. and Grant 81200843 to Y.Y.), from National Basic Research Program of China (973 Program, Grant 2012CB518001, to R.D.Y.), and from the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant 20120073110069, to R.D.Y. and Grant 20120073120091, to Y.Y.). The authors declare no competing financial interests.

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  1. School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China

    Yang Yu & Richard D. Ye

  2. Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL, 60612, USA

    Richard D. Ye

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Yu, Y., Ye, R.D. Microglial Aβ Receptors in Alzheimer’s Disease. Cell Mol Neurobiol 35, 71–83 (2015). https://doi.org/10.1007/s10571-014-0101-6

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