Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes.

ABSTRACT:

Background

Amongst risk alleles associated with late-onset Alzheimer's disease (AD), those that converged on the regulation of microglia activity have emerged as central to disease progression. Yet, how canonical amyloid-β (Aβ) and tau pathologies regulate microglia subtypes during the progression of AD remains poorly understood.

Methods

We use single-cell RNA-sequencing to profile microglia subtypes from mice exhibiting both Aβ and tau pathologies across disease progression. We identify novel microglia subtypes that are induced in response to both Aβ and tau pathologies in a disease-stage-specific manner. To validate the observation in AD mouse models, we also generated a snRNA-Seq dataset from the human superior frontal gyrus (SFG) and entorhinal cortex (ERC) at different

SUBMITTER: Kim DW 

PROVIDER: S-EPMC9762062 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature