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In vivo visualization of propagating α-synuclein pathologies in mouse and marmoset models by a bimodal imaging probe, C05-05

Maiko Ono, Manami Takahashi, Aki Shimozawa, Masayuki Fujinaga, Wakana Mori, Yuji Nagai, Koki Mimura, Takeharu Minamihisamatsu, Shoko Uchida, Masafumi Shimojo, Yuhei Takado, Hiroyuki Takuwa, Naruhiko Sahara, Ming-Rong Zhang, View ORCID ProfileTakafumi Minamimoto, Masato Hasegawa, Makoto Higuchi
doi: https://doi.org/10.1101/2020.10.23.349860
Maiko Ono
1National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
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  • For correspondence: ono.maiko@qst.go.jp
Manami Takahashi
1National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
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Aki Shimozawa
2Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan
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Masayuki Fujinaga
1National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
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Wakana Mori
1National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
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Yuji Nagai
1National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
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Koki Mimura
1National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
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Takeharu Minamihisamatsu
1National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
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Shoko Uchida
1National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
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Masafumi Shimojo
1National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
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Yuhei Takado
1National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
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Hiroyuki Takuwa
1National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
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Naruhiko Sahara
1National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
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Ming-Rong Zhang
1National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
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Takafumi Minamimoto
1National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
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  • ORCID record for Takafumi Minamimoto
Masato Hasegawa
2Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan
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Makoto Higuchi
1National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan
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SUMMARY

Deposition of intracellular α-synuclein fibrils is implicated in neurodegenerative parkinsonian disorders, while high-contrast in vivo detection of α-synuclein depositions has been unsuccessful in animal models and humans. Here, we have developed a bimodal imaging probe, C05-05, for visualizing α-synuclein inclusions in the brains of living animals modeling α-synuclein propagation. In vivo optical and PET imaging of a mouse model demonstrated sensitive detection of α-synuclein aggregates by C05-05, revealing a dynamic propagation of fibrillogenesis along neural pathways followed by disruptions of these structures. Moreover, longitudinal 18F-C05-05-PET of a marmoset model captured widespread dissemination of fibrillary pathologies accompanied by neurodegeneration detected by dopamine transporter PET. In addition, in vitro assays demonstrated the high-affinity binding of 18F-C05-05 to α-synuclein versus other protein pathologies in human brain tissues. Collectively, we propose a new imaging technology enabling etiological and therapeutic assessments of α-synuclein pathogenesis at nonclinical levels, highlighting the applicability of C05-05 to clinical PET.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted October 23, 2020.
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In vivo visualization of propagating α-synuclein pathologies in mouse and marmoset models by a bimodal imaging probe, C05-05
Maiko Ono, Manami Takahashi, Aki Shimozawa, Masayuki Fujinaga, Wakana Mori, Yuji Nagai, Koki Mimura, Takeharu Minamihisamatsu, Shoko Uchida, Masafumi Shimojo, Yuhei Takado, Hiroyuki Takuwa, Naruhiko Sahara, Ming-Rong Zhang, Takafumi Minamimoto, Masato Hasegawa, Makoto Higuchi
bioRxiv 2020.10.23.349860; doi: https://doi.org/10.1101/2020.10.23.349860
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In vivo visualization of propagating α-synuclein pathologies in mouse and marmoset models by a bimodal imaging probe, C05-05
Maiko Ono, Manami Takahashi, Aki Shimozawa, Masayuki Fujinaga, Wakana Mori, Yuji Nagai, Koki Mimura, Takeharu Minamihisamatsu, Shoko Uchida, Masafumi Shimojo, Yuhei Takado, Hiroyuki Takuwa, Naruhiko Sahara, Ming-Rong Zhang, Takafumi Minamimoto, Masato Hasegawa, Makoto Higuchi
bioRxiv 2020.10.23.349860; doi: https://doi.org/10.1101/2020.10.23.349860

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