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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

研究成果: ジャーナルへの寄稿学術論文査読

抄録

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.

本文言語英語
ページ(範囲)42-58.e8
ジャーナルNeuron
109
1
DOI
出版ステータス出版済み - 06-01-2021
外部発表はい

All Science Journal Classification (ASJC) codes

  • 神経科学一般

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