High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer's and Non-Alzheimer's Disease Tauopathies

Kenji Tagai; Maiko Ono; Manabu Kubota; Soichiro Kitamura; Keisuke Takahata; Chie Seki; Yuhei Takado; Hitoshi Shinotoh; Yasunori Sano; Yasuharu Yamamoto; Kiwamu Matsuoka; Hiroyuki Takuwa; Masafumi Shimojo; Manami Takahashi; Kazunori Kawamura; Tatsuya Kikuchi; Maki Okada; Haruhiko Akiyama; Hisaomi Suzuki; Mitsumoto Onaya; Takahiro Takeda; Kimihito Arai; Nobutaka Arai; Nobuyuki Araki; Yuko Saito; John Q. Trojanowski; Virginia M.Y. Lee; Sushil K. Mishra; Yoshiki Yamaguchi; Yasuyuki Kimura; Masanori Ichise; Yutaka Tomita; Ming Rong Zhang; Tetsuya Suhara; Masahiro Shigeta; Naruhiko Sahara; Makoto Higuchi; Hitoshi Shimada

doi:10.1016/j.neuron.2020.09.042

High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer's and Non-Alzheimer's Disease Tauopathies

Kenji Tagai, Maiko Ono, Manabu Kubota, Soichiro Kitamura, Keisuke Takahata, Chie Seki, Yuhei Takado, Hitoshi Shinotoh, Yasunori Sano, Yasuharu Yamamoto, Kiwamu Matsuoka, Hiroyuki Takuwa, Masafumi Shimojo, Manami Takahashi, Kazunori Kawamura, Tatsuya Kikuchi, Maki Okada, Haruhiko Akiyama, Hisaomi Suzuki, Mitsumoto OnayaTakahiro Takeda, Kimihito Arai, Nobutaka Arai, Nobuyuki Araki, Yuko Saito, John Q. Trojanowski, Virginia M.Y. Lee, Sushil K. Mishra, Yoshiki Yamaguchi, Yasuyuki Kimura, Masanori Ichise, Yutaka Tomita, Ming Rong Zhang, Tetsuya Suhara, Masahiro Shigeta, Naruhiko Sahara, Makoto Higuchi, Hitoshi Shimada

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

167 Citations (Scopus)

Abstract

A panel of radiochemicals has enabled in vivo positron emission tomography (PET) of tau pathologies in Alzheimer's disease (AD), although sensitive detection of frontotemporal lobar degeneration (FTLD) tau inclusions has been unsuccessful. Here, we generated an imaging probe, PM-PBB3, for capturing diverse tau deposits. In vitro assays demonstrated the reactivity of this compound with tau pathologies in AD and FTLD. We could also utilize PM-PBB3 for optical/PET imaging of a living murine tauopathy model. A subsequent clinical PET study revealed increased binding of ¹⁸F-PM-PBB3 in diseased patients, reflecting cortical-dominant AD and subcortical-dominant progressive supranuclear palsy (PSP) tau topologies. Notably, the in vivo reactivity of ¹⁸F-PM-PBB3 with FTLD tau inclusion was strongly supported by neuropathological examinations of brains derived from Pick's disease, PSP, and corticobasal degeneration patients who underwent PET scans. Finally, visual inspection of ¹⁸F-PM-PBB3-PET images was indicated to facilitate individually based identification of diverse clinical phenotypes of FTLD on a neuropathological basis.

Original language	English
Pages (from-to)	42-58.e8
Journal	Neuron
Volume	109
Issue number	1
DOIs	https://doi.org/10.1016/j.neuron.2020.09.042
Publication status	Published - 06-01-2021
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Neuroscience

Access to Document

10.1016/j.neuron.2020.09.042

Cite this

Tagai, K., Ono, M., Kubota, M., Kitamura, S., Takahata, K., Seki, C., Takado, Y., Shinotoh, H., Sano, Y., Yamamoto, Y., Matsuoka, K., Takuwa, H., Shimojo, M., Takahashi, M., Kawamura, K., Kikuchi, T., Okada, M., Akiyama, H., Suzuki, H., ... Shimada, H. (2021). High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer's and Non-Alzheimer's Disease Tauopathies. Neuron, 109(1), 42-58.e8. https://doi.org/10.1016/j.neuron.2020.09.042

@article{2024ea2156aa4220a83abbb2e8a0e98d,

title = "High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer's and Non-Alzheimer's Disease Tauopathies",

abstract = "A panel of radiochemicals has enabled in vivo positron emission tomography (PET) of tau pathologies in Alzheimer's disease (AD), although sensitive detection of frontotemporal lobar degeneration (FTLD) tau inclusions has been unsuccessful. Here, we generated an imaging probe, PM-PBB3, for capturing diverse tau deposits. In vitro assays demonstrated the reactivity of this compound with tau pathologies in AD and FTLD. We could also utilize PM-PBB3 for optical/PET imaging of a living murine tauopathy model. A subsequent clinical PET study revealed increased binding of 18F-PM-PBB3 in diseased patients, reflecting cortical-dominant AD and subcortical-dominant progressive supranuclear palsy (PSP) tau topologies. Notably, the in vivo reactivity of 18F-PM-PBB3 with FTLD tau inclusion was strongly supported by neuropathological examinations of brains derived from Pick's disease, PSP, and corticobasal degeneration patients who underwent PET scans. Finally, visual inspection of 18F-PM-PBB3-PET images was indicated to facilitate individually based identification of diverse clinical phenotypes of FTLD on a neuropathological basis.",

keywords = "Alzheimer's disease, PET, Pick's disease, corticobasal degeneration, frontotemporal lobar degeneration, in vivo imaging, progressive supranuclear palsy, tauopathies, tauopathy mouse model, translational research",

author = "Kenji Tagai and Maiko Ono and Manabu Kubota and Soichiro Kitamura and Keisuke Takahata and Chie Seki and Yuhei Takado and Hitoshi Shinotoh and Yasunori Sano and Yasuharu Yamamoto and Kiwamu Matsuoka and Hiroyuki Takuwa and Masafumi Shimojo and Manami Takahashi and Kazunori Kawamura and Tatsuya Kikuchi and Maki Okada and Haruhiko Akiyama and Hisaomi Suzuki and Mitsumoto Onaya and Takahiro Takeda and Kimihito Arai and Nobutaka Arai and Nobuyuki Araki and Yuko Saito and Trojanowski, {John Q.} and Lee, {Virginia M.Y.} and Mishra, {Sushil K.} and Yoshiki Yamaguchi and Yasuyuki Kimura and Masanori Ichise and Yutaka Tomita and Zhang, {Ming Rong} and Tetsuya Suhara and Masahiro Shigeta and Naruhiko Sahara and Makoto Higuchi and Hitoshi Shimada",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2021",

month = jan,

day = "6",

doi = "10.1016/j.neuron.2020.09.042",

language = "English",

volume = "109",

pages = "42--58.e8",

journal = "Neuron",

issn = "0896-6273",

publisher = "Cell Press",

number = "1",

}

Tagai, K, Ono, M, Kubota, M, Kitamura, S, Takahata, K, Seki, C, Takado, Y, Shinotoh, H, Sano, Y, Yamamoto, Y, Matsuoka, K, Takuwa, H, Shimojo, M, Takahashi, M, Kawamura, K, Kikuchi, T, Okada, M, Akiyama, H, Suzuki, H, Onaya, M, Takeda, T, Arai, K, Arai, N, Araki, N, Saito, Y, Trojanowski, JQ, Lee, VMY, Mishra, SK, Yamaguchi, Y, Kimura, Y, Ichise, M, Tomita, Y, Zhang, MR, Suhara, T, Shigeta, M, Sahara, N, Higuchi, M & Shimada, H 2021, 'High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer's and Non-Alzheimer's Disease Tauopathies', Neuron, vol. 109, no. 1, pp. 42-58.e8. https://doi.org/10.1016/j.neuron.2020.09.042

TY - JOUR

T1 - High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer's and Non-Alzheimer's Disease Tauopathies

AU - Tagai, Kenji

AU - Ono, Maiko

AU - Kubota, Manabu

AU - Kitamura, Soichiro

AU - Takahata, Keisuke

AU - Seki, Chie

AU - Takado, Yuhei

AU - Shinotoh, Hitoshi

AU - Sano, Yasunori

AU - Yamamoto, Yasuharu

AU - Matsuoka, Kiwamu

AU - Takuwa, Hiroyuki

AU - Shimojo, Masafumi

AU - Takahashi, Manami

AU - Kawamura, Kazunori

AU - Kikuchi, Tatsuya

AU - Okada, Maki

AU - Akiyama, Haruhiko

AU - Suzuki, Hisaomi

AU - Onaya, Mitsumoto

AU - Takeda, Takahiro

AU - Arai, Kimihito

AU - Arai, Nobutaka

AU - Araki, Nobuyuki

AU - Saito, Yuko

AU - Trojanowski, John Q.

AU - Lee, Virginia M.Y.

AU - Mishra, Sushil K.

AU - Yamaguchi, Yoshiki

AU - Kimura, Yasuyuki

AU - Ichise, Masanori

AU - Tomita, Yutaka

AU - Zhang, Ming Rong

AU - Suhara, Tetsuya

AU - Shigeta, Masahiro

AU - Sahara, Naruhiko

AU - Higuchi, Makoto

AU - Shimada, Hitoshi

PY - 2021/1/6

Y1 - 2021/1/6

N2 - A panel of radiochemicals has enabled in vivo positron emission tomography (PET) of tau pathologies in Alzheimer's disease (AD), although sensitive detection of frontotemporal lobar degeneration (FTLD) tau inclusions has been unsuccessful. Here, we generated an imaging probe, PM-PBB3, for capturing diverse tau deposits. In vitro assays demonstrated the reactivity of this compound with tau pathologies in AD and FTLD. We could also utilize PM-PBB3 for optical/PET imaging of a living murine tauopathy model. A subsequent clinical PET study revealed increased binding of 18F-PM-PBB3 in diseased patients, reflecting cortical-dominant AD and subcortical-dominant progressive supranuclear palsy (PSP) tau topologies. Notably, the in vivo reactivity of 18F-PM-PBB3 with FTLD tau inclusion was strongly supported by neuropathological examinations of brains derived from Pick's disease, PSP, and corticobasal degeneration patients who underwent PET scans. Finally, visual inspection of 18F-PM-PBB3-PET images was indicated to facilitate individually based identification of diverse clinical phenotypes of FTLD on a neuropathological basis.

AB - A panel of radiochemicals has enabled in vivo positron emission tomography (PET) of tau pathologies in Alzheimer's disease (AD), although sensitive detection of frontotemporal lobar degeneration (FTLD) tau inclusions has been unsuccessful. Here, we generated an imaging probe, PM-PBB3, for capturing diverse tau deposits. In vitro assays demonstrated the reactivity of this compound with tau pathologies in AD and FTLD. We could also utilize PM-PBB3 for optical/PET imaging of a living murine tauopathy model. A subsequent clinical PET study revealed increased binding of 18F-PM-PBB3 in diseased patients, reflecting cortical-dominant AD and subcortical-dominant progressive supranuclear palsy (PSP) tau topologies. Notably, the in vivo reactivity of 18F-PM-PBB3 with FTLD tau inclusion was strongly supported by neuropathological examinations of brains derived from Pick's disease, PSP, and corticobasal degeneration patients who underwent PET scans. Finally, visual inspection of 18F-PM-PBB3-PET images was indicated to facilitate individually based identification of diverse clinical phenotypes of FTLD on a neuropathological basis.

KW - Alzheimer's disease

KW - PET

KW - Pick's disease

KW - corticobasal degeneration

KW - frontotemporal lobar degeneration

KW - in vivo imaging

KW - progressive supranuclear palsy

KW - tauopathies

KW - tauopathy mouse model

KW - translational research

UR - http://www.scopus.com/inward/record.url?scp=85096134586&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85096134586&partnerID=8YFLogxK

U2 - 10.1016/j.neuron.2020.09.042

DO - 10.1016/j.neuron.2020.09.042

M3 - Article

C2 - 33125873

AN - SCOPUS:85096134586

SN - 0896-6273

VL - 109

SP - 42-58.e8

JO - Neuron

JF - Neuron

IS - 1

ER -

High-Contrast In Vivo Imaging of Tau Pathologies in Alzheimer's and Non-Alzheimer's Disease Tauopathies

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this