Brain regional susceptibility to tauopathy in individuals at risk for chronic traumatic encephalopathy

INTRODUCTION: Chronic traumatic encephalopathy (CTE) is a tauopathy linked to repetitive head impacts. Factors influencing brain regional susceptibility to tau deposition and spreading remain unclear. METHODS: We used three datasets: [18F]flortaucipir positron emission tomography (PET) in 157 former professional American football players and 53 controls (DIAGNOSE CTE); cortical myelin water fractions (MWF) in 50 healthy individuals (Myelin Water Atlas); and white matter (WM) tract MWF and functional connectivity (FC) in 100 healthy individuals (Human Connectome Project). We tested associations between tau-PET uptake and covariance in football players and typical cortical gray matter (GM) MWF, WM tract MWF, and FC. RESULTS: Cortical regions with lower typical GM MWF showed higher tau-PET uptake (β = −0.399, p = 0.001). WM tracts with lower typical MWF were associated with higher tau-PET covariance (β = −0.238, p < 0.001). Higher typical FC was associated with higher tau-PET covariance (β = 0.447, p < 0.001). DISCUSSION: In former football players at risk for CTE, regional susceptibility to tau deposition may be driven by low myelin and high FC.