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

TitleMicroglial Phagocytosis: A Disease-Associated Process Emerging from Alzheimer's Disease Genetics.
Publication TypeJournal Article
Year of Publication2020
AuthorsPodleśny-Drabiniok A, Marcora E, Goate AM
JournalTrends Neurosci
Date Published2020 12
KeywordsAlzheimer Disease, Genome-Wide Association Study, Humans, Microglia, Neurodegenerative Diseases, Phagocytosis

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.

Pubmed Link
Alternate JournalTrends Neurosci
PubMed ID33127097

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