AV-1451 TAU-PET IN CLINICAL VARIANTS OF PROGRESSIVE SUPRANUCLEAR PALSY

Abstract

Different clinical variants of progressive supranuclear palsy (PSP) have been described, the most common of which is Richardson’s syndrome. The relationship between these clinical variants and pathology is heterogeneous, with all variants associated with tau pathology but with varying patterns of tau deposition within, and across, brain regions. Tau-PET imaging using AV-1451 demonstrates striking uptake in Alzheimer’s disease (AD), although it is unclear whether uptake is observed in the different variants of PSP. We aimed to determine whether tau deposition can be identified on AV-1451 tau-PET in different clinical variants of PSP compared to cognitively normal (CN) subjects and to compare the degree of uptake with that observed in Alzheimer’s disease (AD). Six subjects representing four clinical variants of PSP (Richardson’s syndrome n=3, pure akinesia with gait freezing (PAGF) n=1, primary progressive apraxia of speech (PPAOS) n=1, and post-surgical PSP n=1) underwent tau-PET imaging with AV-1451. These subjects were compared to 101 age-matched CN subjects and 19 subjects with AD. Regional tau-PET uptake was calculated for nine regions typically associated with tau deposition in PSP (midbrain, caudate, putamen, pallidum, supplementary motor area, superior frontal lobe, pre and post central cortex, and thalamus). The PSP subjects showed evidence for subtle elevated tau-PET uptake compared to CN subjects across all regions. Uptake was particularly evident in midbrain, pallidum, supplementary motor area and precentral cortex (Figure). The degree of tau-PET uptake in PSP was lower than AD across all regions except midbrain, pallidum and thalamus. Subtle regional differences were observed between the different clinical variants of PSP. Uptake was generally the highest in those with Richardson’s syndrome across all regions, except for precentral cortex and supplementary motor area which showed highest uptake in PPAOS. PAGF predominantly involved basal ganglia and post-surgical PSP showed subtle uptake in midbrain and thalamus.