Mertk promotes early microglial-mediated synaptic engulfment in Alzheimer's disease.

ABSTRACT: Rationale: Synaptic deficits occur prior to the emergence of Aβ plaques and tau pathology in Alzheimer's disease (AD). Dysregulated microglia excessively prune synapses, leading to synaptic loss. While microglia phagocytic receptor Mertk participates in synaptic pruning, the role of Mertk in driving early synaptic loss in AD remains elusive. Methods: Single-cell RNA sequencing (scRNA-seq) was used to analyze transcriptional changes of microglia in early stage of AD mice. Mertk-mediated synaptic engulfment was investigated both in vivo and in vitro. Results: Phagocytic-associated microglia with upregulated Mertk were identified in the early stage of AD mice. Dysregulated synaptic pruning by microglia caused hippocampal synaptic loss and memory deficits in

SUBMITTER: Wu Y 

PROVIDER: S-EPMC12679373 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature