Reduced [18F]flortaucipir retention in white matter hyperintensities compared to normal-appearing white matter

Recent research has suggested the use of white matter (WM) reference regions for longitudinal tau-PET imaging. However, tau tracers display affinity β-sheet structure formed by myelin, and thus WM lesions might influence tracer retention. Here, we explored whether tau-sensitive [18F]flortaucipir shows reduced retention in hyperintensities (WMH) how this changes over time. We included 707 participants from Alzheimer’s Disease Neuroimaging Initiative with available [18F]flortaucipir-PET structural FLAIR MRI scans. segments WMH were automatically delineated scans, respectively. standardized uptake value ratios (SUVR) normal-appearing (NAWM) calculated using inferior cerebellar grey as region, a 3-mm erosion was applied to combined NAWM masks avoid partial volume effects. Longitudinal SUVR estimated linear mixed models. The percent variance WM-referenced cortical SUVRs explained region R2 coefficient. Compared NAWM, areas displayed significantly SUVR, independent cognitive impairment or Aβ status (mean difference = 0.14 p < 0.001). Older age associated lower both (− 0.002 SUVR/year, 0.005) 0.004 Longitudinally, decreased 0.008 0.03) even more so 0.02 Between 17% 66% region. decreases time is influenced presence WMH, supporting hypothesis that partially myelin-dependent. These findings have implications