Microglial Phagocytosis: A Disease-Associated Process Emerging from Alzheimer's Disease Genetics

被引：126

作者：

Podlesny-Drabiniok, Anna ^{[1
,2
]}

Marcora, Edoardo ^{[1
,2
]}

Goate, Alison M. ^{[1
,2
]}

机构：

[1] Icahn Sch Med Mt Sinai, Dept Neurosci, Ronald M Loeb Ctr Alzheimers Dis, New York, NY 10029 USA

[2] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA

来源：

TRENDS IN NEUROSCIENCES | 2020年 / 43卷 / 12期

关键词：

AMYLOID PRECURSOR PROTEIN; GENOME-WIDE ASSOCIATION; IDENTIFIES VARIANTS; MISSENSE MUTATIONS; RISK LOCI; A-BETA; PROGRANULIN; ONSET; CD33; METAANALYSIS;

D O I：

10.1016/j.tins.2020.10.002

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Alzheimer's disease (AD) is a debilitating, chronic neurodegenerative disease. Genetic studies involving genome-wide association studies (GWAS) and meta-analysis have discovered numerous genomic loci associated with AD; however, the causal genes and variants remain unidentified in most loci. Integration of GWAS signals with epigenomic annotations has demonstrated that AD risk variants are enriched in myeloid-specific enhancers, implicating myeloid cells in AD etiology. AD risk variants in these regulatory elements modify disease susceptibility by regulating the expression of genes that play crucial roles in microglial phagocytosis. Several of these AD risk genes are specifically expressed in myeloid cells, whereas others are ubiquitously expressed but are regulated by AD risk variants within myeloid enhancers in a cell type-specific manner. We discuss the impact of established AD risk variants on microglial phagocytosis and debris processing via the endolysosomal system.

引用

页码：965 / 979

页数：15

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