%0 Journal Article
%T Imaging α-synuclein pathologies in animal models and patients with Parkinson's and related diseases.
%A Endo H
%A Ono M
%A Takado Y
%A Matsuoka K
%A Takahashi M
%A Tagai K
%A Kataoka Y
%A Hirata K
%A Takahata K
%A Seki C
%A Kokubo N
%A Fujinaga M
%A Mori W
%A Nagai Y
%A Mimura K
%A Kumata K
%A Kikuchi T
%A Shimozawa A
%A Mishra SK
%A Yamaguchi Y
%A Shimizu H
%A Kakita A
%A Takuwa H
%A Shinotoh H
%A Shimada H
%A Kimura Y
%A Ichise M
%A Suhara T
%A Minamimoto T
%A Sahara N
%A Kawamura K
%A Zhang MR
%A Hasegawa M
%A Higuchi M
%J Neuron
%V 112
%N 15
%D 2024 Aug 7
%M 38843838
%F 18.688
%R 10.1016/j.neuron.2024.05.006
%X Deposition of α-synuclein fibrils is implicated in Parkinson's disease (PD) and dementia with Lewy bodies (DLB), while in vivo detection of α-synuclein pathologies in these illnesses has been challenging. Here, we have developed a small-molecule ligand, C05-05, for visualizing α-synuclein deposits in the brains of living subjects. In vivo optical and positron emission tomography (PET) imaging of mouse and marmoset models demonstrated that C05-05 captured a dynamic propagation of fibrillogenesis along neural pathways, followed by disruptions of these structures. High-affinity binding of 18F-C05-05 to α-synuclein aggregates in human brain tissues was also proven by in vitro assays. Notably, PET-detectable 18F-C05-05 signals were intensified in the midbrains of PD and DLB patients as compared with healthy controls, providing the first demonstration of visualizing α-synuclein pathologies in these illnesses. Collectively, we propose a new imaging technology offering neuropathology-based translational assessments of PD and allied disorders toward diagnostic and therapeutic research and development.