PT  - JOURNAL ARTICLE
AU  - Ono, Maiko
AU  - Takahashi, Manami
AU  - Shimozawa, Aki
AU  - Fujinaga, Masayuki
AU  - Mori, Wakana
AU  - Nagai, Yuji
AU  - Mimura, Koki
AU  - Minamihisamatsu, Takeharu
AU  - Uchida, Shoko
AU  - Shimojo, Masafumi
AU  - Takado, Yuhei
AU  - Takuwa, Hiroyuki
AU  - Sahara, Naruhiko
AU  - Zhang, Ming-Rong
AU  - Minamimoto, Takafumi
AU  - Hasegawa, Masato
AU  - Higuchi, Makoto
TI  - <em>In vivo</em> visualization of propagating α-synuclein pathologies in mouse and marmoset models by a bimodal imaging probe, C05-05
AID  - 10.1101/2020.10.23.349860
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.10.23.349860
4099  - http://biorxiv.org/content/early/2020/10/23/2020.10.23.349860.short
4100  - http://biorxiv.org/content/early/2020/10/23/2020.10.23.349860.full
AB  - 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 StatementThe authors have declared no competing interest.