Assessment of Tau Pathology as Measured by (18)F-THK5317 and (18)F-Flortaucipir PET and Their Relation to Brain Atrophy and Cognition in Alzheimer’s Disease

BACKGROUND: In Alzheimer’s disease (AD), the abnormal aggregation of hyperphosphorylated tau leads to synaptic dysfunction and neurodegeneration. Recently developed tau PET imaging tracers are candidate biomarkers for diagnosis and staging of AD. OBJECTIVE: We aimed to investigate the discriminative ability of (18)F-THK5317 and (18)F-flortaucipir tracers and brain atrophy at different stages of AD, and their respective associations with cognition. METHODS: Two cohorts, each including 29 participants (healthy controls [HC], prodromal AD, and AD dementia patients), underwent (18)F-THK5317 or (18)F-flortaucipir PET, T1-weighted MRI, and neuropsychological assessment. For each subject, we quantified regional (18)F-THK5317 and (18)F-flortaucipir uptake within six bilateral and two composite regions of interest. We assessed global brain atrophy for each individual by quantifying the brain volume index, a measure of brain volume-to-cerebrospinal fluid ratio. We then quantified the discriminative ability of regional (18)F-THK5317, (18)F-flortaucipir, and brain volume index between diagnostic groups, and their associations with cognition in patients. RESULTS: Both (18)F-THK5317 and (18)F-flortaucipir outperformed global brain atrophy in discriminating between HC and both prodromal AD and AD dementia groups. (18)F-THK5317 provided the highest discriminative ability between HC and prodromal AD groups. (18)F-flortaucipir performed best at discriminating between prodromal and dementia stages of AD. Across all patients, both tau tracers were predictive of RAVL learning, but only (18)F-flortaucipir predicted MMSE. CONCLUSION: Our results warrant further in vivo head-to-head and antemortem-postmortem evaluations. These validation studies are needed to select tracers with high clinical validity as biomarkers for early diagnosis, prognosis, and disease staging, which will facilitate their incorporation in clinical practice and therapeutic trials.