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

Hironobu Endo; Maiko Ono; Yuhei Takado; Kiwamu Matsuoka; Manami Takahashi; Kenji Tagai; Yuko Kataoka; Kosei Hirata; Keisuke Takahata; Chie Seki; Naomi Kokubo; Masayuki Fujinaga; Wakana Mori; Yuji Nagai; Koki Mimura; Katsushi Kumata; Tatsuya Kikuchi; Aki Shimozawa; Sushil K. Mishra; Yoshiki Yamaguchi; Hiroshi Shimizu; Akiyoshi Kakita; Hiroyuki Takuwa; Hitoshi Shinotoh; Hitoshi Shimada; Yasuyuki Kimura; Masanori Ichise; Tetsuya Suhara; Takafumi Minamimoto; Naruhiko Sahara; Kazunori Kawamura; Ming Rong Zhang; Masato Hasegawa; Makoto Higuchi

doi:10.1016/j.neuron.2024.05.006

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

Hironobu Endo, Maiko Ono, Yuhei Takado, Kiwamu Matsuoka, Manami Takahashi, Kenji Tagai, Yuko Kataoka, Kosei Hirata, Keisuke Takahata, Chie Seki, Naomi Kokubo, Masayuki Fujinaga, Wakana Mori, Yuji Nagai, Koki Mimura, Katsushi Kumata, Tatsuya Kikuchi, Aki Shimozawa, Sushil K. Mishra, Yoshiki YamaguchiHiroshi Shimizu, Akiyoshi Kakita, Hiroyuki Takuwa, Hitoshi Shinotoh, Hitoshi Shimada, Yasuyuki Kimura, Masanori Ichise, Tetsuya Suhara, Takafumi Minamimoto, Naruhiko Sahara, Kazunori Kawamura, Ming Rong Zhang, Masato Hasegawa, Makoto Higuchi

Research output: Contribution to journal › Article › peer-review

49 Citations (Scopus)

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.

Original language	English
Pages (from-to)	2540-2557.e8
Journal	Neuron
Volume	112
Issue number	15
DOIs	https://doi.org/10.1016/j.neuron.2024.05.006
Publication status	Published - 07-08-2024
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Neuroscience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.neuron.2024.05.006

Cite this

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, S. K., ... Higuchi, M. (2024). Imaging α-synuclein pathologies in animal models and patients with Parkinson's and related diseases. Neuron, 112(15), 2540-2557.e8. https://doi.org/10.1016/j.neuron.2024.05.006

@article{49b9aa381d6f46eaad6152a3d785ccca,

title = "Imaging α-synuclein pathologies in animal models and patients with Parkinson's and related diseases",

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.",

keywords = "PET, Parkinson's disease, dementia with Lewy bodies, in vivo, intravital two-photon microscopy, marmoset model, mouse model, multiple system atrophy, propagation, α-synuclein",

author = "Hironobu Endo and Maiko Ono and Yuhei Takado and Kiwamu Matsuoka and Manami Takahashi and Kenji Tagai and Yuko Kataoka and Kosei Hirata and Keisuke Takahata and Chie Seki and Naomi Kokubo and Masayuki Fujinaga and Wakana Mori and Yuji Nagai and Koki Mimura and Katsushi Kumata and Tatsuya Kikuchi and Aki Shimozawa and Mishra, \{Sushil K.\} and Yoshiki Yamaguchi and Hiroshi Shimizu and Akiyoshi Kakita and Hiroyuki Takuwa and Hitoshi Shinotoh and Hitoshi Shimada and Yasuyuki Kimura and Masanori Ichise and Tetsuya Suhara and Takafumi Minamimoto and Naruhiko Sahara and Kazunori Kawamura and Zhang, \{Ming Rong\} and Masato Hasegawa and Makoto Higuchi",

note = "Publisher Copyright: {\textcopyright} 2024 The Author(s)",

year = "2024",

month = aug,

day = "7",

doi = "10.1016/j.neuron.2024.05.006",

language = "English",

volume = "112",

pages = "2540--2557.e8",

journal = "Neuron",

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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 2024, 'Imaging α-synuclein pathologies in animal models and patients with Parkinson's and related diseases', Neuron, vol. 112, no. 15, pp. 2540-2557.e8. https://doi.org/10.1016/j.neuron.2024.05.006

TY - JOUR

T1 - Imaging α-synuclein pathologies in animal models and patients with Parkinson's and related diseases

AU - Endo, Hironobu

AU - Ono, Maiko

AU - Takado, Yuhei

AU - Matsuoka, Kiwamu

AU - Takahashi, Manami

AU - Tagai, Kenji

AU - Kataoka, Yuko

AU - Hirata, Kosei

AU - Takahata, Keisuke

AU - Seki, Chie

AU - Kokubo, Naomi

AU - Fujinaga, Masayuki

AU - Mori, Wakana

AU - Nagai, Yuji

AU - Mimura, Koki

AU - Kumata, Katsushi

AU - Kikuchi, Tatsuya

AU - Shimozawa, Aki

AU - Mishra, Sushil K.

AU - Yamaguchi, Yoshiki

AU - Shimizu, Hiroshi

AU - Kakita, Akiyoshi

AU - Takuwa, Hiroyuki

AU - Shinotoh, Hitoshi

AU - Shimada, Hitoshi

AU - Kimura, Yasuyuki

AU - Ichise, Masanori

AU - Suhara, Tetsuya

AU - Minamimoto, Takafumi

AU - Sahara, Naruhiko

AU - Kawamura, Kazunori

AU - Zhang, Ming Rong

AU - Hasegawa, Masato

AU - Higuchi, Makoto

PY - 2024/8/7

Y1 - 2024/8/7

N2 - 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.

AB - 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.

KW - PET

KW - Parkinson's disease

KW - dementia with Lewy bodies

KW - in vivo

KW - intravital two-photon microscopy

KW - marmoset model

KW - mouse model

KW - multiple system atrophy

KW - propagation

KW - α-synuclein

UR - https://www.scopus.com/pages/publications/85197033706

UR - https://www.scopus.com/inward/citedby.url?scp=85197033706&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2024.05.006

DO - 10.1016/j.neuron.2024.05.006

M3 - Article

C2 - 38843838

AN - SCOPUS:85197033706

SN - 0896-6273

VL - 112

SP - 2540-2557.e8

JO - Neuron

JF - Neuron

IS - 15

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

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