Research progress in microglia-related susceptibility genes in Alzheimer's disease and their mechanisms
10.13481/j.1671-587X.20250131
- VernacularTitle:阿尔茨海默病中小胶质细胞相关易感基因及其作用机制的研究进展
- Author:
Kuai WANG
1
;
Yu YANG
Author Information
1. 吉林大学第一医院神经内科,吉林长春 130021
- Keywords:
Alzheimer's disease;
Microglia;
Susceptibility genes;
Phagocytosis;
Lipid metabolism;
Immune response
- From:
Journal of Jilin University(Medicine Edition)
2025;51(1):255-265
- CountryChina
- Language:Chinese
-
Abstract:
Microglia,as intrinsic immune cells of the central nervous system,play an immune response function in Alzheimer's disease(AD),which prevents further damages by eliminating abnormal proteins and apoptotic neurons while also leads pathological progression via inducing chronic neuro inflammation.The previous studies have suggested that the functional changes of microglia activation are initiated by AD pathologies.However,the recent genomic studies have challenged this understanding.Large-scale genome-wide association analysis(GWAS)and whole genome/exome sequencing studies have identified more than 70 risk loci of AD.Among these risk loci,most gene variants are involved in encoding microglia function-related molecules or affecting the transcriptional activity of genes associated with the microglial biofunctions.The functional and pathway analysis results have revealed that these risk loci are mainly enriched in signaling pathways regulating microglia phagocytosis,lipid metabolism,and immune response,suggesting that microglia not only act as a"responder"to AD pathologies,but also a"participant"in the development of AD pathogenesis.In-depth studies of these susceptibility genes may further expand our understanding of the regulatory mechanisms and functional spectrum of microglia in AD.This review is based on genetic studies and summarizes the current knowledge of microglial-related susceptibility genes related to AD and their regulatory mechanisms.
