Multiomic single nuclei profiling the mouse hippocampus reveals that ACSS2 confers neuronal resilience to tauopathy
We combine tau seeding with deletion of acetyl-CoA synthetase 2 (ACSS2) to test this enzyme in an Alzheimer's disease model. Loss of ACSS2 exacerbates transcriptional and behavioral responses to tau injection. We observe robust transcriptional dysregulation in pyramidal neurons in the hippocampus. We observe reduced numbers of reelin-producing Cajal-Retzius cells in the hippocampus. Acetate supplementation rescues transcriptional and behavioral responses to tau.
Authors
- Greg Donahue (ORCID: https://orcid.org/0000-0002-2378-1618)
- Mariel Mendoza (ORCID: https://orcid.org/0000-0003-2072-4914)
- Gabor Egervári (ORCID: https://orcid.org/0000-0002-2371-2532)
- Connor Hogan (ORCID: https://orcid.org/0000-0002-6167-9112)
- Nancy M. Bonini (ORCID: https://orcid.org/0000-0003-0226-5291)
- Desi C. Alexander (ORCID: https://orcid.org/0000-0001-8715-2004)
- Hong Xu (ORCID: https://orcid.org/0000-0002-3501-4758)
- Hua Huang
- Shelley Berger
- Ben Garcia
- Virginia Lee
Institutions
- Washington University in St. Louis (US)
- University of the Arts (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2026-02-01
- DOI
- https://doi.org/10.1002/alz.70998
- Citations
- 1
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 32.84
Funders
- Alzheimer's Association
- University of Pennsylvania
- Institute for Translational Medicine and Therapeutics
- National Alliance for Research on Schizophrenia and Depression
- Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation
- National Institutes of Health
- Intellectual and Developmental Disabilities Research Center
- National Cancer Institute
- National Institute of General Medical Sciences
- National Institute of Child Health and Human Development