Beyond <i>p</i> ‐Tau: Unveiling Caspase‐6 Truncated Tau as an Early and Distinct Pathological Marker in Alzheimer's Disease
Our findings challenge the prevailing model that tau PTMs always co-occur with p-tau inclusions in AD. We demonstrate that caspase-6-cleaved tr-tau appears earlier than p-tau in EC and ITG, with a higher burden at early Braak stages. Additionally, tr-tau and p-tau show minimal colocalization throughout disease progression, reinforcing the idea that tr-tau represents a distinct and previously overlooked pathological feature of AD. These results highlight tr-tau as a potential early marker of AD progression and a promising target for therapeutic intervention.
Authors
- Lea T. Grinberg (ORCID: https://orcid.org/0000-0002-6809-0618)
- Renata Elaine Paraízo Leite (ORCID: https://orcid.org/0000-0002-5878-398X)
- Ian Oh
- Song Hua Li
- Salvatore Spina (ORCID: https://orcid.org/0000-0003-3570-9143)
- Andrew J. Ambrose (ORCID: https://orcid.org/0000-0002-2932-4514)
- Michelle R. Arkin (ORCID: https://orcid.org/0000-0002-9366-6770)
- Vítor Ribeiro Paes (ORCID: https://orcid.org/0000-0001-8752-5624)
- Cláudia Kimie Suemoto (ORCID: https://orcid.org/0000-0002-5942-4778)
- Akshay Raju (ORCID: https://orcid.org/0000-0002-6192-3613)
- Prabhleen Kaur (ORCID: https://orcid.org/0000-0002-6994-9914)
- Rushil Jerfy
- Felipe Luiz Pereira
- Roberta Diehl Rodriguez
- Robert Zhang
- William W. Seeley
- Bruce L. Miller
Institutions
- Universidade de São Paulo (BR)
- University of California, San Francisco (US)
- University Memory and Aging Center (US)
- Global Brain Health Institute (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1002/alz70855_106040
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00