The Functions and Phenotypes of Microglia in Alzheimer's Disease

Risako Fujikawa; Makoto Tsuda

doi:10.3390/cells12081207

The Functions and Phenotypes of Microglia in Alzheimer's Disease

Cells. 2023 Apr 21;12(8):1207. doi: 10.3390/cells12081207.

Authors

Risako Fujikawa¹, Makoto Tsuda^{1

2}

Affiliations

¹ Department of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
² Kyushu University Institute for Advanced Study, Fukuoka 819-0395, Japan.

Abstract

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease worldwide, but therapeutic strategies to slow down AD pathology and symptoms have not yet been successful. While attention has been focused on neurodegeneration in AD pathogenesis, recent decades have provided evidence of the importance of microglia, and resident immune cells in the central nervous system. In addition, new technologies, including single-cell RNA sequencing, have revealed heterogeneous cell states of microglia in AD. In this review, we systematically summarize the microglial response to amyloid-β and tau tangles, and the risk factor genes expressed in microglia. Furthermore, we discuss the characteristics of protective microglia that appear during AD pathology and the relationship between AD and microglia-induced inflammation during chronic pain. Understanding the diverse roles of microglia will help identify new therapeutic strategies for AD.

Keywords: Alzheimer’s disease; ApoE; CD11c; DAMs; TREM2; amyloid beta; brain; microglia; monocyte; pain; spinal cord; tau.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / pathology
Central Nervous System / pathology
Humans
Microglia / pathology
Neurodegenerative Diseases* / pathology
Phenotype

Grants and funding

This work was supported by JSPS KAKENHI Grant Numbers JP19H05658, JP20H05900 (M.T.), by JST [Moonshot R and D] [Grant Number JPMJMS2024] (M.T.), and by Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED under Grant Number JP22ama121031 (M.T.).