| Literature DB >> 33125873 |
Kenji Tagai1, Maiko Ono2, Manabu Kubota3, Soichiro Kitamura4, Keisuke Takahata5, Chie Seki2, Yuhei Takado6, Hitoshi Shinotoh7, Yasunori Sano5, Yasuharu Yamamoto5, Kiwamu Matsuoka4, Hiroyuki Takuwa2, Masafumi Shimojo2, Manami Takahashi2, Kazunori Kawamura2, Tatsuya Kikuchi2, Maki Okada2, Haruhiko Akiyama8, Hisaomi Suzuki9, Mitsumoto Onaya10, Takahiro Takeda11, Kimihito Arai11, Nobutaka Arai12, Nobuyuki Araki11, Yuko Saito13, John Q Trojanowski14, Virginia M Y Lee14, Sushil K Mishra15, Yoshiki Yamaguchi16, Yasuyuki Kimura17, Masanori Ichise2, Yutaka Tomita18, Ming-Rong Zhang2, Tetsuya Suhara1, Masahiro Shigeta19, Naruhiko Sahara2, Makoto Higuchi20, Hitoshi Shimada2.
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.Entities:
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
Year: 2020 PMID： 33125873 DOI： 10.1016/j.neuron.2020.09.042
Source DB: PubMed Journal: Neuron ISSN： 0896-6273 Impact factor: 17.173