Imaging α-synuclein pathologies in animal models and patients with Parkinson's and related diseases.

Autor:	Endo H; Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan. Electronic address: endo.hironobu@qst.go.jp., Ono M; Institute for Quantum Life Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Takado Y; Institute for Quantum Life Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Matsuoka K; Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Department of Psychiatry, Nara Medical University, Nara 634-8522, Japan., Takahashi M; Quantum Neuromapping and Neuromodulation Team, Institute for Quantum Life Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Tagai K; Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Department of Psychiatry, The Jikei University School of Medicine, Tokyo 105-8461, Japan., Kataoka Y; Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Hirata K; Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo 113-8510, Japan., Takahata K; Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Department of Psychiatry, Keio University School of Medicine, Tokyo 160-0016, Japan., Seki C; Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Kokubo N; Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Fujinaga M; Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Mori W; Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Nagai Y; Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Mimura K; Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Research Center for Medical and Health Data Science, The Institute of Statistical Mathematics, Tokyo 190-8562, Japan., Kumata K; Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Kikuchi T; Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Shimozawa A; Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan., Mishra SK; Department of BioMolecular Sciences, The University of Mississippi, Oxford, MS 38677, USA., Yamaguchi Y; Division of Structural Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Miyagi Japan., Shimizu H; Department of Pathology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan., Kakita A; Department of Pathology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan., Takuwa H; Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Quantum Neuromapping and Neuromodulation Team, Institute for Quantum Life Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Shinotoh H; Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Neurology Clinic, Chiba 260-0045, Chiba Japan., Shimada H; Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Department of Functional Neurology & Neurosurgery, Center for Integrated Human Brain Science, Brain Research Institute, Niigata University, Niigata 951-8585, Japan., Kimura Y; Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu 474-8511, Aichi, Japan., Ichise M; Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Suhara T; National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Minamimoto T; Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Sahara N; Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Kawamura K; Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Zhang MR; Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan., Hasegawa M; Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan., Higuchi M; Advanced Neuroimaging Center, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba 263-8555, Japan; Department of Neuroetiology and Diagnostic Science, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, Japan.
Jazyk:	angličtina
Zdroj:	Neuron [Neuron] 2024 Aug 07; Vol. 112 (15), pp. 2540-2557.e8. Date of Electronic Publication: 2024 Jun 05.
DOI:	10.1016/j.neuron.2024.05.006
Abstrakt:	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 18 F-C05-05 to α-synuclein aggregates in human brain tissues was also proven by in vitro assays. Notably, PET-detectable 18 F-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. Competing Interests: Declaration of interests M.O., M.-R.Z., and M. Higuchi filed a patent on compounds related to the present report (2019-034997, PCT/JP2020/002607). (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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