Evaluation of the relation between tau protein and white matter structural changes in Alzheimer's disease using fixel-based analysis

Motivation: Studies have suggested that tau deposition-induced neurotoxicity causes progressive white matter (WM) degeneration in Alzheimer's disease (AD) and its prodromal phase; however, this is not yet fully elucidated. Goal(s): To employ fixel-based analysis (FBA) to assess tau-related WM degeneration and its effect to cognitive function. Approach: The WM integrity and cortical tau load were compared across AD, mild cognitive impairment, and cognitive normal subjects using FBA and tau PET. Results: FBA metrics in WM under highly tau-deposited cortex were downward with higher effect sizes in patients. An association between entorhinal tau and cognitive function was mediated by FBA metrics in the parahippocampal cingulum. Impact: Our findings suggest the possibility that neurons were degenerated through prion-like tau propagation along axons and may shed light on future research on mechanisms of cognitive decline in Alzheimer's disease.