High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer's and Non-Alzheimer's Disease Tauopathies

A panel of radiochemicals has enabled in vivo positron emission tomography (PET) of tau pathologies in Alzheimer's disease (AD), although sensitive detection of frontotemporal lobar degeneration (FTLD) tau inclusions has been unsuccessful. Here, we generated an imaging probe, PM-PBB3, for capturing diverse tau deposits. In vitro assays demonstrated the reactivity of this compound with tau pathologies in AD and FTLD. We could also utilize PM-PBB3 for optical/PET imaging of a living murine tauopathy model. A subsequent clinical PET study revealed increased binding of F-18-PM-PBB3 in diseased patients, reflecting cortical-dominant AD and subcortical-dominant progressive supranuclear palsy (PSP) tau topologies. Notably, the in vivo reactivity of F-18-PM-PBB3 with FTLD tau inclusion was strongly supported by neuropathological examinations of brains derived from Pick's disease, PSP, and corticobasal degeneration patients who underwent PET scans. Finally, visual inspection of F-18-PM-PBB3-PET images was indicated to facilitate individually based identification of diverse clinical phenotypes of FTLD on a neuropathological basis.

Automated summary

A panel of radiochemicals for in vivo PET imaging of tau pathologies in AD has been developed, but sensitive detection of FTLD tau inclusions remains challenging. The imaging probe PM-PBB3 successfully captures diverse tau deposits in AD and FTLD, with increased binding observed in diseased patients in a subsequent clinical PET study. Visual inspection of F-18-PM-PBB3-PET images aids in individually based identification of diverse clinical phenotypes of FTLD on a neuropathological basis.