18F-flortaucipir tau PET distinguishes established progressive supranuclear palsy from controls and Parkinson’s disease: A multicenter study



Objective: 18F-flortaucipir (formerly 18F-AV1451 or 18F-T807) binds to neurofibrillary tangles in Alzheimer’s disease (AD), but tissue studies assessing binding to tau aggregates in progressive supranuclear palsy (PSP) have yielded mixed results. We compared in vivo 18F-flortaucipir uptake in patients meeting clinical research criteria for PSP (N=33) to normal controls (N=46) and patients meeting criteria for Parkinson’s disease (PD, N=26).

Methods: Participants underwent MRI and positron emission tomography for amyloid-β (11C-PiB or 18F-florbetapir) and tau (18F-flortaucipir). 18F-flortaucipir Standardized Uptake Value Ratios were calculated (t=80-100 min, cerebellum gray matter reference). Voxelwise and region-of-interest group comparisons were performed in template space, with Receiver Operating Characteristic curve analyses to assess single-subject discrimination. Qualitative comparisons with postmortem tau are reported in one patient who died nine months after 18F-flortaucipir.

Results: Clinical PSP patients showed bilaterally elevated 18F-flortaucipir uptake in globus pallidus, putamen, subthalamic nucleus, midbrain and dentate nucleus relative to controls and PD patients (voxelwise p<0.05 family-wise-error-corrected). Globus pallidus binding best distinguished PSP patients from controls and PD (Area Under the Curve (AUC)=0.872 vs. controls, AUC=0.893 vs. PD). PSP clinical severity did not correlate with 18F-flortaucipir in any region. A patient with clinical PSP and pathological diagnosis of corticobasal degeneration had severe tau-pathology in PSP-related brain structures with good correspondence between in vivo 18F-flortaucipir and postmortem tau neuropathology.

Interpretation: 18F-flortaucipir uptake was elevated in PSP versus controls and PD patients in a pattern consistent with the expected distribution of tau pathology. This article is protected by copyright. All rights reserved.


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