Neuropathological correlations of 18F-florzolotau PET in a case with pick's disease.

Abstract

Background: 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.

Case presentation: 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.

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