TY - JOUR
T1 - Imaging of tau pathology in a tauopathy mouse model and in alzheimer patients compared to normal controls
AU - Maruyama, Masahiro
AU - Shimada, Hitoshi
AU - Suhara, Tetsuya
AU - Shinotoh, Hitoshi
AU - Ji, Bin
AU - Maeda, Jun
AU - Zhang, Ming Rong
AU - Trojanowski, John Q.
AU - Lee, Virginia M.Y.
AU - Ono, Maiko
AU - Masamoto, Kazuto
AU - Takano, Harumasa
AU - Sahara, Naruhiko
AU - Iwata, Nobuhisa
AU - Okamura, Nobuyuki
AU - Furumoto, Shozo
AU - Kudo, Yukitsuka
AU - Chang, Qing
AU - Saido, Takaomi C.
AU - Takashima, Akihiko
AU - Lewis, Jada
AU - Jang, Ming Kuei
AU - Aoki, Ichio
AU - Ito, Hiroshi
AU - Higuchi, Makoto
N1 - Funding Information:
The authors thank Mr. T. Minamihisamatsu and Mr. Y. Matsuba for technical assistance, the staff of the Molecular Probe Group, National Institute of Radiological Sciences, for support with radiosynthesis, Dr. Y. Yoshiyama at National Hospital Organization Chiba-East Hospital for his support on clinical PET studies, and Dr. T. Iwatsubo at the University of Tokyo and Dr. H. Inoue at Kyoto University for their critical discussions. This work was supported in part by grants from the National Institute on Aging of the National Institutes of Health (AG10124 and AG17586) (to J.Q.T. and V. M.-Y.L.), Grants-in-Aid for Japan Advanced Molecular Imaging Program, Young Scientists (21791158) (to M.M.), Scientific Research (B) (23390235) (to M.H.), Core Research for Evolutional Science and Technology (to T.S.), Scientific Research on Innovative Areas (“Brain Environment”) (23111009) (to M.H.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, Thomas H. Maren Junior Investigator Fund from College of Medicine, University of Florida (to N.S.), and research fund of Belfer Neurodegeneration Consortium (to Q.C. and M.-K.J.). M.M., H. Shimada, T.S., M.-R.Z., and M.H. are named as inventors on a patent application 0749006WO1, claiming subject matter related to the results described in this paper.
PY - 2013/9/18
Y1 - 2013/9/18
N2 - 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
AB - 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
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U2 - 10.1016/j.neuron.2013.07.037
DO - 10.1016/j.neuron.2013.07.037
M3 - Article
C2 - 24050400
AN - SCOPUS:84884273839
VL - 79
SP - 1094
EP - 1108
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 6
ER -