Distinct mechanistic pathways of early tauopathy revealed by <i>MAPT</i> mutations
Schematic representation comparing two trajectories of tau pathology. The S305N mutation promotes a 4R isoform shift, cytoskeletal damage and synapse loss, and accumulation of soluble hyperphosphorylated tau. Tau remains soluble even at old ages. In contrast, the P301S mutation generates hypophosphorylated, seed-competent tau that forms fibrils. The effect of amyloid is slow in the S305N, but results in accelerated acceleration of pathology in the P301S. Figure made with Biorender.com .
Authors
- Martha Foiani (ORCID: https://orcid.org/0000-0003-4157-2606)
- Timothy J.Y. Birkle (ORCID: https://orcid.org/0000-0001-6395-8142)
- Saisha Patel
- Nayab Fatima (ORCID: https://orcid.org/0000-0002-8146-2674)
- Sumi Bez (ORCID: https://orcid.org/0000-0002-8971-5103)
- Eliona Tsefou (ORCID: https://orcid.org/0000-0002-4643-2584)
- Neil A. Ranson (ORCID: https://orcid.org/0000-0002-3640-5275)
- Elena Camporesi (ORCID: https://orcid.org/0000-0003-1044-0192)
- Naoto Watamura (ORCID: https://orcid.org/0000-0001-7971-7378)
- Sheena E. Radford (ORCID: https://orcid.org/0000-0002-3079-8039)
- Helen Davies (ORCID: https://orcid.org/0000-0001-6102-256X)
- G. Brinkmalm
- Chris Goulbourne
- Raja Nirujogi
- Alessia Santambrogio
- K.E. Duff
Institutions
- Nathan Kline Institute for Psychiatric Research (US)
- University of Leeds (GB)
- University of Wisconsin–Madison (US)
- Queen Mary University of London (GB)
- University of Cambridge (GB)
- RIKEN Center for Brain Science (JP)
- MRC Protein Phosphorylation and Ubiquitylation Unit (GB)
- UK Dementia Research Institute (GB)
- University College London (GB)
- University of Gothenburg (SE)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-02-16
- DOI
- https://doi.org/10.64898/2026.02.14.705716
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00