A brain‐derived tau oligomer polymorph is associated with cognitive resilience to Alzheimer's disease
Non-demented with Alzheimer's neuropathology (NDAN) brain-derived tau oligomers (BDTOs) exhibit distinct, more stable structural polymorphs compared to those from Alzheimer's disease (AD). NDAN-BDTOs are larger, more protease resistant, and less toxic in cell and hippocampal slice models. Both NDAN- and AD-BDTOs seed tau aggregation, but NDAN-BDTOs promote formation of less toxic assemblies. Structural stability of NDAN-BDTOs may contribute to cognitive resilience despite AD pathology. Mimicking non-toxic tau polymorphs could represent a novel therapeutic strategy for AD.
Authors
- Shrinath Kadamangudi (ORCID: https://orcid.org/0009-0009-8427-4837)
- Giulio Taglialatela (ORCID: https://orcid.org/0000-0003-4795-447X)
- Rakez Kayed (ORCID: https://orcid.org/0000-0001-6216-8640)
- Michela Marcatti (ORCID: https://orcid.org/0000-0003-1921-4626)
- Anna Fracassi (ORCID: https://orcid.org/0000-0001-9310-8982)
- Jutatip Guptarak
- Pietro Scaduto (ORCID: https://orcid.org/0000-0001-8197-615X)
- Batbayar Tumurbaatar
- Wen Ru Zhang
- Regan J. Schuetze
Institutions
- The University of Texas Medical Branch at Galveston (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-08-01
- DOI
- https://doi.org/10.1002/alz.70550
- Citations
- 2
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 2.33
Funders
- Alzheimer's Association
- Oregon Health and Science University
- National Institutes of Health
- National Institute on Aging