Microglia in Alzheimer's disease at single-cell level. Are there common patterns in humans and mice?

Alzheimer's disease (AD) is characterized by extracellular aggregates of amyloid β peptides, intraneuronal tau aggregates, and neuronal death. This pathology triggers activation of microglia. Because variants of genes expressed in microglia correlate with AD risk, microglial response to patholo...

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Vydáno v:The Journal of experimental medicine Ročník 218; číslo 9
Hlavní autoři: Chen, Yun, Colonna, Marco
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 06.09.2021
Témata:
Aging - physiology
Alzheimer Disease - genetics
Alzheimer Disease - pathology
Animals
Disease Models, Animal
Gene Expression
Histocompatibility Antigens Class II - genetics
Histocompatibility Antigens Class II - metabolism
Humans
Interferon Type I - genetics
Interferon Type I - metabolism
Mice
Microglia - pathology
Neurons - pathology
Single-Cell Analysis
ISSN:1540-9538, 1540-9538
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Shrnutí:Alzheimer's disease (AD) is characterized by extracellular aggregates of amyloid β peptides, intraneuronal tau aggregates, and neuronal death. This pathology triggers activation of microglia. Because variants of genes expressed in microglia correlate with AD risk, microglial response to pathology plausibly impacts disease course. In mouse AD models, single-cell RNA sequencing (scRNA-seq) analyses delineated this response as progressive conversion of homeostatic microglia into disease-associated microglia (DAM); additional reactive microglial populations have been reported in other models of neurodegeneration and neuroinflammation. We review all of these microglial signatures, highlighting four fundamental patterns: DAM, IFN-microglia, MHC-II microglia, and proliferating microglia. We propose that all reported microglia populations are either just one or a combination, depending on the clustering strategy applied and the disease model. We further review single-nucleus RNA sequencing (snRNA-seq) data from human AD specimens and discuss reasons for parallels and discrepancies between human and mouse transcriptional profiles. Finally, we outline future directions for delineating the microglial impact in AD pathogenesis.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1540-9538
1540-9538
DOI:10.1084/jem.20202717