Shifting paradigms: The central role of microglia in Alzheimer's disease.
ABCA7
APOE
Alzheimer's disease
Brain
CD33
GWAS
MS4A4A
MS4A6A
Microglia
Neurodegeneration
Neuropathology
Single-cell
Single-nuclei
TREM2
Transcriptomic
Journal
Neurobiology of disease
ISSN: 1095-953X
Titre abrégé: Neurobiol Dis
Pays: United States
ID NLM: 9500169
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
07
12
2019
revised:
01
05
2020
accepted:
10
06
2020
pubmed:
15
6
2020
medline:
6
8
2021
entrez:
15
6
2020
Statut:
ppublish
Résumé
Recent human genetic studies have challenged long standing hypotheses about the chain of events in Alzheimer's disease (AD), as the identification of genetic risk factors in microglial genes supports a causative role for microglia in the disease. Parallel transcriptome and histology studies at the single-cell level revealed a rich palette of microglial states affected by disease status and genetic risk factors. Taken together, those findings support microglia dysfunction as a central mechanism in AD etiology and thus the therapeutic potential of modulating microglial activity for AD treatment. Here we review how human genetic studies discovered microglial AD risk genes, such as TREM2, CD33, MS4A and APOE, and how experimental studies are beginning to decipher the cellular functions of some of these genes. Our review also focuses on recent transcriptomic studies of human microglia from postmortem tissue to critically assess areas of similarity and dissimilarity between human and mouse models currently in use in order to better understand the biology of innate immunity in AD.
Identifiants
pubmed: 32535152
pii: S0969-9961(20)30237-0
doi: 10.1016/j.nbd.2020.104962
pii:
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
104962Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.