TY - JOUR TI - Bundle-specific associations between white matter microstructure and Aβ and tau pathology in preclinical Alzheimer’s disease AU - Pichet Binette, Alexa AU - Theaud, Guillaume AU - Rheault, François AU - Roy, Maggie AU - Collins, D Louis AU - Levin, Johannes AU - Mori, Hiroshi AU - Lee, Jae Hong AU - Farlow, Martin Rhys AU - Schofield, Peter AU - Chhatwal, Jasmeer P AU - Masters, Colin L AU - Benzinger, Tammie AU - Morris, John AU - Bateman, Randall AU - Breitner, John CS AU - Poirier, Judes AU - Gonneaud, Julie AU - Descoteaux, Maxime AU - Villeneuve, Sylvia AU - DIAN Study Group AU - PREVENT-AD Research Group A2 - Makin, Tamar R A2 - Barense, Morgan A2 - Bokde, Arun A2 - Wearn, Alfie A2 - Grydeland, Hakon VL - 10 PY - 2021 DA - 2021/05/13 SP - e62929 C1 - eLife 2021;10:e62929 DO - 10.7554/eLife.62929 UR - https://doi.org/10.7554/eLife.62929 AB - 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. KW - PET KW - diffusion MRI KW - free-water KW - uncinate fasciculus KW - cingulum JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -