Development of novel PET probes for α-synuclein pathologies

Makoto Higuchi

National Institutes for Quantum Science and Technology

Depositions of α-synuclein fibrils are neuropathological hallmarks of Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), while assemblies of tau isoforms with four repeat domains (4RTs) are known to accumulate in a subset of frontotemporal lobar degeneration disorders, such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), which are causative of atypical parkinsonian syndromes.　We developed PBB3 and PM-PBB3 as positron emission tomography (PET) probes for 4RT aggregates and have succeeded in capturing characteristic tau pathologies in PSP and CBD.　Classes of chemicals originating from these tau probes, including C05-05 and SPAL-T-06, were shown to have high affinities for α-synuclein deposits and have enabled visualization of α-synuclein lesions in animal models of disseminating α-synuclein pathologies and patients with MSA. Application of these compounds to PD and DLB cases is currently underway.

Address correspondence to Dr. Makoto Higuchi, National Institutes for Quantum Science and Technology(4-9-1 Anagawa, Inage, Chiba 263-8555, Japan)