Transcriptomics

Dataset Information

0

The APOE-R136S mutation protects against APOE4-driven Tau pathology, neurodegeneration and neuroinflammation


ABSTRACT: Apolipoprotein E4 (APOE4) is the strongest genetic risk factor for late-onset Alzheimer’s disease (LOAD), leading to earlier age of clinical onset and exacerbating pathologies. There is a critical need to identify protective targets. Recently, a rare APOE variant, APOE3-R136S (Christchurch), was found to protect against early-onset AD in a PSEN1-E280A carrier. We sought to determine if the R136S mutation also protects against APOE4-driven effects in LOAD. We generated tauopathy mouse and human iPSC-derived neuron models carrying human APOE4 with the homozygous or heterozygous R136S mutation. We found that the homozygous R136S mutation rescued APOE4-driven Tau pathology, neurodegeneration, and neuroinflammation. The heterozygous R136S mutation partially protected against APOE4-driven neurodegeneration and neuroinflammation, but not Tau pathology. Single-nucleus RNA-sequencing revealed that the APOE4-R136S mutation increased disease-protective and diminished disease-associated cell populations in a gene dose-dependent manner. Thus, the APOE-R136S mutation protects against APOE4-driven AD pathologies, providing a target for therapeutic development against AD.

ORGANISM(S): Mus musculus

PROVIDER: GSE217854 | GEO | 2023/09/21

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

| PRJNA901027 | ENA
2023-01-06 | GSE221215 | GEO
2023-05-03 | GSE193513 | GEO
2024-10-25 | GSE248020 | GEO
2022-11-30 | GSE206368 | GEO
2021-04-13 | GSE164507 | GEO
2023-12-08 | GSE242693 | GEO
2023-12-08 | GSE242180 | GEO
2023-07-20 | PXD036416 | Pride
2022-10-20 | GSE215446 | GEO