The relationship between amyloid-β peptide spectrum and the spastic paraparesis phenotype in autosomal dominant Alzheimer’s disease
Our analysis reveals a robust association between elevated Aβ43 levels and SP development in PSEN1 mutation carriers. While this correlation does not establish causation, the distinct impact of SP-associated mutations on γ-secretase function, resulting in elevated Aβ43 production, suggests that mutation-specific mechanisms may underlie clinical heterogeneity in ADAD, with potential implications for biomarker and translational research.
Authors
- Lucía Chávez‐Gutiérrez (ORCID: https://orcid.org/0000-0002-8239-559X)
- Thomas Enzlein (ORCID: https://orcid.org/0000-0003-1789-4090)
- Mohamed Belal Hamed (ORCID: https://orcid.org/0000-0002-6383-4147)
- Katarzyna Marta Zoltowska (ORCID: https://orcid.org/0000-0001-5853-3465)
- Carsten Hopf (ORCID: https://orcid.org/0000-0003-0802-6451)
- José María Pinazo Bandera (ORCID: https://orcid.org/0009-0000-1104-7232)
- Natalie S. Ryan (ORCID: https://orcid.org/0000-0003-0361-7455)
Institutions
- Technische Hochschule Mannheim (DE)
- Allen Institute for Brain Science (US)
- Vlaams Instituut voor Biotechnologie (BE)
- UK Dementia Research Institute (GB)
- National Research Centre (EG)
- National Hospital for Neurology and Neurosurgery (GB)
- VIB-KU Leuven Center for Brain & Disease Research (BE)
- University College London (GB)
Publication Details
- Journal
- Alzheimer s Research & Therapy
- Published
- 2025-11-26
- DOI
- https://doi.org/10.1186/s13195-025-01896-3
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00