Spatiotemporal Tau Accumulation and Its Clinical Impact on PSP: Longitudinal Florzolotau (18F) PET

BackgroundFlorzolotau (18F) positron emission tomography (florzolotau PET) enables high-contrast in vivo detection of four-repeat tau pathology in progressive supranuclear palsy (PSP), but whether longitudinal tau imaging reflects disease progression remains unclear. ObjectivesTo explore longitudinal tau accumulation using florzolotau PET and evaluate its association with clinical progression in PSP. MethodsA total of 26 patients with PSP (18 Richardsons syndrome [PSP-RS], 8 non-RS) and 10 age- and sex-matched healthy controls (HCs) underwent florzolotau PET, MRI, and clinical assessments at baseline and after 1 year. Regional standardized uptake value ratios (SUVR) were extracted across 57 regions of interest. Partial least squares (PLS) multivariate analyses revealed regions with elevated baseline SUVR and longitudinal increase ({Delta}SUVR) in PSP relative to HCs, alongside regions where {Delta}SUVR was associated with changes in PSP Rating Scale scores. ResultsAt baseline, tau deposition was most prominent in the globus pallidus (GP) and midbrain in patients with PSP. Longitudinal tau increases were observed in the GP, frontoparietal cortex, and cerebellum, whereas minimal progression was observed in the midbrain. GP tau accumulation exhibited the strongest association with clinical progression in the PLS model among PSP-RS and a univariate correlation (Spearmans {rho} = 0.674, p = 0.002). ConclusionsThis study provides in vivo evidence of the spatiotemporal progression of tau pathology in PSP. In the GP, tau accumulation emerges early and continues to rise with clinical deterioration. These findings support the utility of florzolotau PET for monitoring disease progression and as a biological outcome measure in tau-targeted therapeutic trials.