Multimodal In Vivo and Post-mortem Assessments of Tau in Lewy Body Disorders

Abstract We compared the regional retention of 18F-flortaucipir in twenty patients with Lewy Body disorders (LBD), twelve matched Alzheimer’s disease patients with positive amyloid PET scans (AD+Aβ), and fifteen healthy-controls with negative amyloid PET scans (HC-Aβ) and the association in LBD between retention and CSF tau, cognitive performance, and neuropathological tau at autopsy. The LBD cohort was stratified using an established Aβ42 cut-off of 192pg/ml to enrich for groups likely harboring tau pathology (LBD+Aβ=11, LBD-Aβ=9). 18F-flortaucipir retention was higher in LBD+AB than HC-Aβ in five, largely temporal-parietal, cortical regions whereas LBD-Aβ had elevations in one cortical region with sparing of medial temporal areas. Higher retention was associated with higher CSF total-tau levels (p=0.04), poorer domain-specific cognitive performance (p=0.02-0.04), and greater severity of neuropathological tau in corresponding regions. We conclude that while 18F-flortaucipir retention in LBD is intermediate between healthy-controls and AD, retention relates to cognitive impairment, CSF total-tau, and neuropathological tau. Future work in larger autopsy-validated cohorts are needed to define LBD-specific tau biomarker profiles.