Neuropathological correlations of ¹⁸F-florzolotau PET in a case with Pick’s disease

Pick's disease (PiD) is classified as frontotemporal lobar degeneration with pathological tau aggregates. Positron emission tomography (PET) with ¹⁸F-florzolotau provides high-contrast imaging of diverse tau fibrils. While our previous work demonstrated the detectability of three repeat (3R) tau pathology by ¹⁸F-florzolotau PET in an autopsy-confirmed PiD patient, its potential for quantitative assessment of 3R tau aggregates in living individuals remains unclear. In this study, we analyzed correlations between in vivo ¹⁸F-florzolotau retentions and postmortem neuropathological data across brain regions in the same case with PiD.

The patient was 60 years of age at the time of death and had been diagnosed with behavioral variant frontotemporal dementia. The patient underwent ¹⁸F-florzolotau PET one year prior to death and was given the pathological diagnosis of PiD by brain autopsy. Regional tau pathology was assessed using Bodian's silver staining and immunohistochemistry with a monoclonal antibody (AT8). Histopathological assays revealed abundant intraneuronal Pick bodies along with neuropil threads in frontotemporal and other brain areas. In the cerebral cortex, AT8-positive areas exhibited a significant positive correlation with ¹⁸F-florzolotau binding in the corresponding regions (Pearson's r = 0.81, p < 0.001) estimated as standardized uptake value ratio corrected for partial volume effect. In contrast, no such associations were found in subcortical structures. Furthermore, a substantial proportion of Pick bodies displayed fluorescence co-labelled with florzolotau and AT8 antibodies.

Collectively, the present findings support the capability of ¹⁸F-florzolotau PET for the in vivo quantification of 3R tau fibrils.