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

• Published in: eLife 2021-05, Vol.10
• Main Authors: Pichet Binette, Alexa, Theaud, Guillaume, Rheault, François, Roy, Maggie, Collins, D Louis, Levin, Johannes, Mori, Hiroshi, Lee, Jae Hong, Farlow, Martin Rhys, Schofield, Peter, Chhatwal, Jasmeer P, Masters, Colin L, Benzinger, Tammie, Morris, John, Bateman, Randall, Breitner, John Cs, Poirier, Judes, Gonneaud, Julie, Descoteaux, Maxime, Villeneuve, Sylvia
• Format: Article
• Language: English
• Subjects: Adult; Age; Aged; Aged, 80 and over; Algorithms; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Anisotropy; Asymptomatic; Automation; Blood pressure; Brain; Cingulum; Cognitive ability; Dementia; diffusion MRI; Diffusion Tensor Imaging; Female; free-water; Humans; Investigations; Magnetic resonance imaging; Male; Middle Aged; Mutation; Neurodegenerative diseases; Neuroimaging; Neuroscience; Older people; Pathology; PET; Positron emission tomography; Substantia alba; Tau protein; tau Proteins - metabolism; uncinate fasciculus; White Matter - pathology; White Matter - ultrastructure; β-Amyloid
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.62929

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.