NAD+ hydrolase Sarm1 is a key driver of synapse degeneration and memory loss in Alzheimer’s disease
Sarm1 is enriched at presynaptic dystrophies and correlated with Aβ.Genetic deletion of Sarm1 prevents synapse degeneration in AD.Sarm1 depletion is sufficient to reverse synaptic dysfunction and memory loss.Sarm1 depletion reduces Aβ burden and neuroinflammationC1q--MERTK axis acts downstream of synaptic Sarm1 activation.
Authors
- Q. Liu
- Michael Abayomi Abiola (ORCID: https://orcid.org/0000-0001-9872-8718)
- Sandeep Kumar Kotturu (ORCID: https://orcid.org/0000-0002-0549-4455)
- Fan Fan (ORCID: https://orcid.org/0000-0003-1463-3610)
- Xuelin Lou
- Xiaojie Liu
- Prince Joshi
Institutions
- Medical College of Wisconsin (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2025-12-23
- DOI
- https://doi.org/10.64898/2025.12.21.695860
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health