{Reference Type}: Journal Article
{Title}: Imaging α-synuclein pathologies in animal models and patients with Parkinson's and related diseases.
{Author}: Endo H;Ono M;Takado Y;Matsuoka K;Takahashi M;Tagai K;Kataoka Y;Hirata K;Takahata K;Seki C;Kokubo N;Fujinaga M;Mori W;Nagai Y;Mimura K;Kumata K;Kikuchi T;Shimozawa A;Mishra SK;Yamaguchi Y;Shimizu H;Kakita A;Takuwa H;Shinotoh H;Shimada H;Kimura Y;Ichise M;Suhara T;Minamimoto T;Sahara N;Kawamura K;Zhang MR;Hasegawa M;Higuchi M;
{Journal}: Neuron
{Volume}: 112
{Issue}: 15
{Year}: 2024 Aug 7
{Factor}: 18.688
{DOI}: 10.1016/j.neuron.2024.05.006
{Abstract}: 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.