Back to Search
Start Over
Alzheimer's Patient Microglia Exhibit Enhanced Aging and Unique Transcriptional Activation.
- Source :
-
Cell reports [Cell Rep] 2020 Jun 30; Vol. 31 (13), pp. 107843. - Publication Year :
- 2020
-
Abstract
- Damage-associated microglia (DAM) profiles observed in Alzheimer's disease (AD)-related mouse models reflect an activation state that could modulate AD risk or progression. To learn whether human AD microglia (HAM) display a similar profile, we develop a method for purifying cell types from frozen cerebrocortical tissues for RNA-seq analysis, allowing better transcriptome coverage than typical single-nucleus RNA-seq approaches. The HAM profile we observe bears little resemblance to the DAM profile. Instead, HAM display an enhanced human aging profile, in addition to other disease-related changes such as APOE upregulation. Analyses of whole-tissue RNA-seq and single-cell/nucleus RNA-seq datasets corroborate our findings and suggest that the lack of DAM response in human microglia occurs specifically in AD tissues, not other neurodegenerative settings. These results, which can be browsed at http://research-pub.gene.com/BrainMyeloidLandscape, provide a genome-wide picture of microglial activation in human AD and highlight considerable differences between mouse models and human disease.<br />Competing Interests: Declaration of Interests T.G.B. and G.E.S. participated in this study under a contracted research agreement. All other authors are current or former employees of the pharmaceutical company Genentech, Inc..<br /> (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Aged
Aged, 80 and over
Animals
Databases, Genetic
Female
Frontal Lobe pathology
Frozen Sections
Gene Expression Profiling
Genetic Predisposition to Disease
Heterografts
Humans
Male
Mice
Monocytes metabolism
Multiple Sclerosis pathology
Phenotype
Reproducibility of Results
Risk Factors
Temporal Lobe pathology
Alzheimer Disease genetics
Alzheimer Disease pathology
Cellular Senescence genetics
Microglia metabolism
Microglia pathology
Transcriptional Activation genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 31
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 32610143
- Full Text :
- https://doi.org/10.1016/j.celrep.2020.107843