Journal article

Bundle-specific associations between white matter microstructure and Ab and tau pathology in preclinical Alzheimer's disease

Alexa Pichet Binette, Guillaume Theaud, Francois Rheault, Maggie Roy, D Louis Collins, Johannes Levin, Hiroshi Mori, Jae Hong Lee, Martin Rhys Farlow, Peter Schofield, Jasmeer P Chhatwal, Colin L Masters, Tammie Benzinger, John Morris, Randall Bateman, John Cs Breitner, Judes Poirier, Julie Gonneaud, Maxime Descoteaux, Sylvia Villeneuve



Beta-amyloid (Aβ) and tau proteins, the pathological hallmarks of Alzheimer's disease (AD), are believed to spread through connected regions of the brain. Combining diffusion imaging and positron emission tomography, we investigated associations between white matter microstructure specifically in bundles connecting regions where Aβ or tau accumulates and pathology. We focused on free-water-corrected diffusion measures in the anterior cingulum, posterior cingulum, and uncinate fasciculus in cognitively normal older adults at risk of sporadic AD and presymptomatic mutation carriers of autosomal dominant AD. In Aβ-positive or tau-positive groups, lower tissue fractional anisotropy and higher me..

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Awarded by Dominantly Inherited Alzheimer's Network (DIAN) - National Institute on Aging (NIA)

Funding Acknowledgements

We wish to acknowledge the staff of PREVENT-AD as well as of the Brain Imaging Centre of the Douglas Mental Health University Institute and of the PET unit of the McConnell Brain Imaging Centre of the Montreal Neurological Institute, and members of the SCIL lab. A full listing of members of the PREVENT-AD Research Group can be found at[2020-06-30]. We would also like to acknowledge the participants of the PREVENT-AD cohort for dedicating their time and energy to helping us collect these data. Thank you to the Neuroinformatics Chair of the Universite de Sherbrooke for supporting neuroscience research. Data collection and sharing for this project was supported by The Dominantly Inherited Alzheimer's Network (DIAN, UF1AG032438) funded by the National Institute on Aging (NIA), the German Center for Neurodegenerative Diseases (DZNE), Raul Carrea Institute for Neurological Research (FLENI), partial support by the Research and Development Grants for Dementia from Japan Agency for Medical Research and Development, AMED, and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI). This manuscript has been reviewed by DIAN Study investigators for scientific content and consistency of data interpretation with previous DIAN Study publications. We acknowledge the altruism of the participants and their families and contributions of the DIAN research and support staff at each of the participating sites for their contributions to this study.