Imaging of tau pathology in a tauopathy mouse model and in alzheimer patients compared to normal controls

Masahiro Maruyama, Hitoshi Shimada, Tetsuya Suhara, Hitoshi Shinotoh, Bin Ji, Jun Maeda, Ming Rong Zhang, John Q. Trojanowski, Virginia M.Y. Lee, Maiko Ono, Kazuto Masamoto, Harumasa Takano, Naruhiko Sahara, Nobuhisa Iwata, Nobuyuki Okamura, Shozo Furumoto, Yukitsuka Kudo, Qing Chang, Takaomi C. Saido, Akihiko TakashimaJada Lewis, Ming Kuei Jang, Ichio Aoki, Hiroshi Ito, Makoto Higuchi

Research output: Contribution to journalArticlepeer-review

505 Citations (Scopus)

Abstract

Accumulation of intracellular tau fibrils has been the focus of research on the mechanisms of neurodegeneration in Alzheimer@s disease (AD) and related tauopathies. Here, we have developed a class of tau ligands, phenyl/pyridinyl-butadienyl-benzothiazoles/benzothiazoliums (PBBs), for visualizing diverse tau inclusions in brains of living patients with AD or non-AD tauopathies and animal models of these disorders. Invivo optical and positron emission tomographic (PET) imaging of a transgenic mouse model demonstrated sensitive detection oftau inclusions by PBBs. A pyridinated PBB, [11C]PBB3, was next applied in a clinical PET study, and its robust signal in the AD hippocampus wherein tau pathology is enriched contrasted strikingly with that of a senile plaque radioligand, [11C]Pittsburgh Compound-B ([11C]PIB). [11C]PBB3-PET data were also consistent with the spreading of tau pathology with AD progression. Furthermore, increased [11C]PBB3 signals were found in a corticobasal syndrome patient negative for [11C]PIB-PET

Original languageEnglish
Pages (from-to)1094-1108
Number of pages15
JournalNeuron
Volume79
Issue number6
DOIs
Publication statusPublished - 2013 Sep 18

ASJC Scopus subject areas

  • Neuroscience(all)

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