GEO series

Astrocytic Sox9 preserves cognitive function in models of Alsheimer's Disease

GSE294933 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 6 samples Submitted 2026/01/06 Platform GPL21626

Summary

Astrocytes play essential roles in the brain and their dysfunction is associated with nearly every form of neurological disease. Despite their ubiquity, our knowledge of how astrocytes contribute to disease pathogenesis is incomplete, accordingly harnessing their biology towards therapeutics remains a major challenge. Here we show that the transcription factor Sox9 plays a context specific role in maintaining astrocyte function and circuit activity in the aging hippocampus and Alzheimer’s Disease (AD) models. We found that Sox9 overexpression in astrocytes in AD models clears existing amyloid beta (Aβ) plaques and preserves cognitive function. Mechanistically, Sox9 promotes the phagocytosis of Aβ plaques by astrocytes through the regulation of the phagocytic receptor MEGF10, which is sufficient to preserve cognitive function in AD models. Collectively, these studies highlight new roles for astrocytic Sox9 during aging and AD, while identifying Sox9-MEGF10 signaling as a prospective astrocyte-based therapeutic approach to ameliorate cognitive decline in neurodegenerative disease.

Published in

Astrocytic Sox9 overexpression in Alzheimer's disease mouse models promotes Aβ plaque phagocytosis and preserves cognitive function

Choi DJ, Murali S, Kwon W et al. · Nature neuroscience 2026 · PMID 41272323 · doi:10.1038/s41593-025-02115-w

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Direct links to NCBI, no account and no request form: the whole study as GSE294933_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 6 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1252062 and SRA study SRP579458. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41272323) ↗

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