Human microglia differentially respond to β-amyloid, tau, and combined Alzheimer's disease pathologies in vivo.

ABSTRACT:

Introduction

Recent studies have identified important species-dependent differences in the response of microglia to β-amyloid (Aβ) pathology. Yet, whether human microglia also interact differently with the pathognomonic combination of amyloid and tau pathologies that occur in Alzheimer's disease (AD) remains unclear.

Methods

We generated a xenotolerant mouse model of AD that develops both plaque and tangle pathologies, transplanted stem cell-derived microglial progenitors and examined the interactions between human microglia and AD pathologies with scRNA sequencing, immunohistochemistry, and in vitro modeling.

Results

The combined amyloid and tau pathologies induced robust type-I interferon and proinflammatory cytokine responses, as well as an increased adoption of a

SUBMITTER: Coburn MA 

PROVIDER: S-EPMC12635866 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature