Alzheimer's Patient Microglia Exhibit Enhanced Aging and Unique Transcriptional Activation.

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 spe

SUBMITTER: Srinivasan K 

PROVIDER: S-EPMC7422733 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature