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

TitleBundle-specific associations between white matter microstructure and Aβ and tau pathology in preclinical Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2021
AuthorsBinette APichet, Theaud G, Rheault F, Roy M, D Collins L, Levin J, Mori H, Lee JHong, Farlow MRhys, Schofield P, Chhatwal JP, Masters CL, Benzinger T, Morris J, Bateman R, Breitner JCS, Poirier J, Gonneaud J, Descoteaux M, Villeneuve S
Corporate AuthorsDIAN Study Group, PREVENT-AD Research Group
JournalElife
Volume10
Date Published2021 05 13
ISSN2050-084X
KeywordsAdult, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Diffusion Tensor Imaging, Female, Humans, Male, Middle Aged, Positron-Emission Tomography, tau Proteins, White Matter
Abstract

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 mean diffusivity related to greater Aβ and tau burden in both cohorts. Associations were found in the posterior cingulum and uncinate fasciculus in preclinical sporadic AD, and in the anterior and posterior cingulum in presymptomatic mutation carriers. These results suggest that microstructural alterations accompany pathological accumulation as early as the preclinical stage of both sporadic and autosomal dominant AD.

DOI10.7554/eLife.62929
Alternate JournalElife
PubMed ID33983116
PubMed Central IDPMC8169107
Grant ListPJT-148963 / / CIHR / Canada
UF1 AG032438 / AG / NIA NIH HHS / United States
PJT-162091 / / CIHR / Canada