Valiltramiprosate Effects on Microstructural Integrity of Grey and White Matter in APOE4/4 Homozygotes with Early AD and their Correlations to Clinical Outcomes: MRI Mean Diffusivity Results from the 78‐Week APOLLOE4 Phase 3 Trial
Consistent with valiltramiprosate's effects on brain volumes, its effects on microstructural integrity were most prominent in the MCI subgroup that showed lower diffusivity in the cingulate cortex and major hippocampal outflow tracts. This microstructural preservation correlated significantly with preservation of HV/CT and with clinical benefits. These findings support valiltramiprosate's proposed mechanism: inhibiting oligomer formation may directly protect synapses/axons from damage, thus slowing neurodegeneration at a microstructural level and contributing to macrostructural preservation of brain volumes and clinical benefit.
Authors
- John A. Hey (ORCID: https://orcid.org/0000-0002-5104-6231)
- Emer MacSweeney
- Adem Albayrak (ORCID: https://orcid.org/0000-0002-6436-3164)
- Susan Flint
- Chris J. Conklin
- David Watson
- Duygu Tosun (ORCID: https://orcid.org/0000-0001-5174-3910)
- Martin Tolar (ORCID: https://orcid.org/0000-0002-3910-091X)
- Madhura Ingalhalikar (ORCID: https://orcid.org/0000-0002-4809-8559)
- Patrick Kesslak
- Aidan Power
- Earvin Liang
- Susan Abushakra
- Arthur Rosenthal
- Anton P. Porsteinsson
- P. Murali Doraiswamy
- Sharon Cohen
- Marwan N. Sabbagh
Institutions
- Department of Health and Social Care (GB)
- San Francisco VA Medical Center (US)
- Barrow Neurological Institute (US)
- Duke University (US)
- Toronto Public Health (CA)
- Alzheimer’s Disease Neuroimaging Initiative (US)
- Houston Perinatal Associates (US)
- Framingham State University (US)
- University of Rochester (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1002/alz70861_108716
- Primary Topic
- Advanced Neuroimaging Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 0.00