Florzolotau (18F) PET provides in-vivo measures of tau pathology in progressive supranuclear palsy: An imaging-postmortem correlation study

The clinical diagnosis of 4-repeat tauopathies, including progressive supranuclear palsy (PSP) and corticobasal degeneration, remains challenging. Although patients may present with characteristic clinical features suggestive of these diseases, discrepancies frequently arise between antemortem diagnosis and postmortem pathological findings. Reliable biomarkers for in vivo detection of tau deposition are therefore urgently needed. We report a case of a man in his 60s who developed progressive gait disturbance and cerebellar ataxia. Based on clinical findings, PSP with predominant cerebellar ataxia (PSP-C) was suspected, and tau positron emission tomography (PET) using florzolotau (18F) ([18F]florzolotau) was performed. The PET scan revealed marked tracer retention in the upper brainstem, bilateral diencephalon, and basal ganglia, consistent with the PSP-C phenotype. The patient died of aspiration pneumonia three years after the first visit, and a neuropathological examination confirmed PSP, showing neuronal and glial tau aggregates, including tufted astrocytes, primarily in the midbrain, pons, dentate nucleus and subthalamic nucleus. To quantitatively assess the concordance between in vivo and postmortem findings, tau burden was measured across 48 representative brain regions using AT8 immunohistochemistry and a binarization-based quantification method. Regional tau pathology presented a strong positive correlation with the standardized uptake value ratio of [18F]florzolotau derived from the antemortem PET data. In conclusion, this study provides direct evidence that [18F]florzolotau-PET accurately reflects the regional distribution of tau pathology in PSP. Our findings support the clinical utility of [18F]florzolotau as a sensitive probe for diagnosing 4-repeat tauopathies and for therapeutic evaluations targeting these disorders.