Identification and therapeutic modulation of a pro-inflammatory subset of disease-associated-microglia in Alzheimer's disease.

ABSTRACT:

Background

Disease-associated-microglia (DAM) represent transcriptionally-distinct and neurodegeneration-specific microglial profiles with unclear significance in Alzheimer's disease (AD). An understanding of heterogeneity within DAM and their key regulators may guide pre-clinical experimentation and drug discovery.

Methods

Weighted co-expression network analysis (WGCNA) was applied to existing microglial transcriptomic datasets from neuroinflammatory and neurodegenerative disease mouse models to identify modules of highly co-expressed genes. These modules were contrasted with known signatures of homeostatic microglia and DAM to reveal novel molecular heterogeneity within DAM. Flow cytometric validation studies were performed to confirm existence of distinct DAM sub-populati

SUBMITTER: Rangaraju S 

PROVIDER: S-EPMC5963076 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature