Mapping the Influence of Amyloid, Tau, and APOE Variants on White Matter Tracts in Alzheimer’s Disease

Motivation: Alzheimer's disease (AD) biomarkers like amyloid, tau, and APOE variants impact brain white matter tracts, potentially revealing AD progression pathways. Goal(s): Examine how these biomarkers affect microstructure of white matter tracts, aiding in AD tracking and prediction. Approach: Using diffusion MRI from 730 ADNI3 participants, we applied BUndle ANalytics (BUAN) tractometry to analyze biomarker-related microstructural differences along specific white matter tracts. Results: Amyloid positivity increased diffusivity in key tracts, tau showed stronger associations with Mean diffusivity (MD) near cortical regions, and APOE ϵ4 carriers exhibited greater microstructural changes. These findings emphasize MD's potential for early detection and monitoring of Alzheimer's disease progression. Impact: Our findings highlight the role of tau, amyloid, and APOE variants in disrupting brain connectivity, shedding light on Alzheimer's disease pathology and localized white matter tract changes.