The relationship 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 degeneration in Alzheimer's disease; however, this has not yet been fully elucidated. Goal(s): To assess tau-related white matter (WM) degeneration in the whole brain and its effects on cognitive function using fixel-based analysis (FBA). Approach: WM integrity and cortical tau load were compared in Alzheimer's disease, mild cognitive impairment, and cognitive normal subjects using FBA and 18F-flortaucipir. Results: FBA metrics in subcortical WM of highly tau-deposited cortex showed degeneration of both micro and macrostructures. An association between entorhinal tau and cognitive function was mediated by FBA metrics in entorhinal subcortical WM. Impact: Our findings suggest the possibility that neurons were degenerated through the propagation of tau along the WM and may shed light on future research on the mechanisms of cognitive decline in Alzheimer's disease.