APOE4 exacerbates glucocorticoid stress hormone-induced tau pathology via mitochondrial dysfunction.

ABSTRACT: APOE4 is the leading genetic risk factor for Alzheimer's disease, and chronic stress is a leading environmental risk factor. Studies suggest that APOE4 confers vulnerability to the behavioral and neuropathological effects of chronic stress, representing a potential mechanism by which this genetic variant accelerates Alzheimer's onset and progression. Whether and how APOE4-mediated stress vulnerability manifests in neurons of the hippocampus, a brain region particularly susceptible to stress and Alzheimer's pathology, remains unexplored. Using a combination of in vivo and in vitro experiments in humanized APOE4 and APOE3 knockin mice and primary hippocampal neurons from these animals, we investigate whether and how APOE4 confers sensit

SUBMITTER: Yu Q 

PROVIDER: S-EPMC11838549 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature