Single‐cell landscape of sex‐specific drivers of Alzheimer's disease
Single-nucleus transcriptomic association analysis identified 2660 sex-specific associations involving 2110 genes with four AD endophenotypes. The majority of female-specific associations link to better endophenotype outcomes were from neurons. Nine female-specific associations were replicated, including ADGRV1 and OR3A3 with Aβ; IFI27L1, LYRM1, STAP2, and TSTD2 with tau; PDYN with global cognition; and TMEM50B with longitudinal cognitive trajectory. Sex-specific effect genes were enriched in the immune-, inflammation-, and damage-related stress-response pathways. Six ITGB1-mediated microglia-specific incoming signals may play roles in female-specific risk for Aβ accumulation.
Authors
- Timothy J. Hohman (ORCID: https://orcid.org/0000-0002-3377-7014)
- Vilas Menon (ORCID: https://orcid.org/0000-0002-4096-8601)
- Logan C. Dumitrescu (ORCID: https://orcid.org/0000-0002-9782-9944)
- AR Dunn
- Mariano I. Gabitto (ORCID: https://orcid.org/0000-0001-6911-344X)
- Catherine C. Kaczorowski (ORCID: https://orcid.org/0000-0001-5430-0816)
- Yiyang Wu
- Philip L. De Jager
- Kyle J. Travaglini
- C. Dirk Keene
- Julie A. Schneider
- David A. A. Bennett
Institutions
- Rush University Medical Center (US)
- University of Washington (US)
- University of Michigan (US)
- Columbia University Irving Medical Center (US)
- Jackson Laboratory (US)
- Allen Institute (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1002/alz.71041
- Citations
- 1
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Nancy and Buster Alvord Endowment
- University of Washington
- Rush University
- National Institutes of Health
- National Institute on Aging