Selective white matter tract vulnerability associated with tau burden in progressive supranuclear palsy and Alzheimer's disease.

Abstract

Progressive supranuclear palsy (PSP) and Alzheimer's disease (AD) exhibit different tau distributions. We compared tract-specific associations between florzolotau(18F) retention, white matter (WM) microstructure, and clinical impairment. Forty-nine patients with PSP, 40 with AD, and 30 cognitively unimpaired controls underwent florzolotau(18F) PET. Tractography evaluated projection and association fibers, including the dentatorubrothalamic tract (DRTT) and superior longitudinal fasciculus (SLF). Regional SUVRs were calculated using WM-PERSI normalization. Associations among uptake, diffusion measures, brain volume, and clinical outcomes were evaluated using covariate-adjusted correlations with Bonferroni correction, partial canonical correlation, and exploratory path analyses. PSP was characterized by predominantly subcortical and brainstem florzolotau(18F) retention and more extensive WM abnormalities, including DRTT involvement. AD showed predominantly cortical retention and microstructural abnormalities of SLF branches. In PSP, regional subcortical uptake was associated with DRTT microstructure, while DRTT mean diffusivity and frontal volume contributed most strongly to the canonical variate associated with motor impairment (canonical correlation = 0.82, p = 0.001). In AD, cortical uptake was associated with SLF microstructure, while cortical volume and SLF mean diffusivity contributed to the canonical variate associated with executive function (canonical correlation = 0.83, p = 0.001). Exploratory path models were consistent with indirect associations involving white matter microstructure and cortical volume. PSP and AD showed distinct patterns of tract vulnerability associated with regional florzolotau(18F) retention and clinical impairment. These cross-sectional findings support further longitudinal investigation of disease-specific network degeneration.