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bioRxiv · 10.1101/2020.10.23.349860

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

Ono, M.·Takahashi, M.·Shimozawa, A.·Fujinaga, M.·Mori, W.·Nagai, Y.·Mimura, K.·Minamihisamatsu, T.·Uchida, S.·Shimojo, M.·Takado, Y.·Takuwa, H.·Sahara, N.·Zhang, M.-R.·Minamimoto, T.·Hasegawa, M.·Higuchi, M.
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Abstract

Deposition of -synuclein fibrils is implicated in Parkinsons disease (PD) and dementia with Lewy bodies (DLB), while in vivo detection of -synuclein pathologies in these illnesses has been challenging. Here, we have developed a small-molecule ligand, C05-05, for visualizing -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 -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 to healthy controls, providing the first demonstration of visualizing -synuclein pathologies in these illnesses. Collectively, we propose a new imaging technology offering neuropathology-based translational assessments of PD and allied disorders towards diagnostic and therapeutic research and development.

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Ono, M., Takahashi, M., Shimozawa, A., Fujinaga, M., Mori, W., Nagai, Y., Mimura, K., Minamihisamatsu, T., Uchida, S., Shimojo, M., Takado, Y., Takuwa, H., Sahara, N., Zhang, M.-R., Minamimoto, T., Hasegawa, M., Higuchi, M.. 2020-10-23. In vivo visualization of propagating α-synuclein pathologies in mouse and marmoset models by a bimodal imaging probe, C05-05. https://doi.org/10.1101/2020.10.23.349860

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