@misc{oai:repo.qst.go.jp:00069813,
 author = {Maruyama, Masahiro and Maeda, Jun and Ki, Hin and Zhang, Ming-Rong and Okauchi, Takashi and Ono, Maiko and Hattori, Satoko and Q., Trojanowski John and M.-Y., Lee Virginia and Fukumura, Toshimitsu and Higuchi, Makoto and Suhara, Tetsuya and 丸山 将浩 and 前田 純 and 季 斌 and 張 明栄 and 岡内 隆 and 小野 麻衣子 and 服部 聡子 and 福村 利光 and 樋口 真人 and 須原 哲也},
 month = {Jul},
 note = {Background: Intracellular inclusions of pathological tau fibrils are hallmark lesions in Alzheimer
's disease (AD) and associated tauopathies, and there has been a growing interest in the mechanistic links between fibrillar tau accumulation and neuronal deterioration. In-vivo visualization of tau lesions would thus serve the preclinical and clinical needs for pursuing the molecular etiology of neurodegenerative disorders and evaluating candidate disease-modifying therapies. This notion has led us to develop imaging agents capable of capturing tau aggregates in a living mouse model of tauopathies.
Methods: An array of fluorescent chemicals were screened by assaying their in-vitro binding to recombinant tau fibrils and neuronal tau inclusions on brain sections from patients with diverse tauopathies and mice transgenic for the pathogenic P301S mutant tau. The selected compounds were intravenously injected into the tau transgenics, and ex-vivo labelings of tau lesions with these agents in excised brain samples were microscopically assessed. Pulse-laser optical and positron emission tomographic (PET) systems were then applied to in-vivo detections of tau pathologies in the transgenic mice with near-infrared fluorescent and 11C-labeled compounds, respectively. The PET data were also supplemented by in-vitro and ex-vivo autoradiographic analyses.
Results: Chemical properties of the compounds such as structural dimensions and hydrophilicities were associated with their affinities for tau inclusions in a wide range of tauopathies as well as transgenics. A class of chemicals sharing the common core structure enabled ex-vivo visualization of aggregates in the transgenic mice. One of these putative imaging agents was suitable for the near-infrared optics, and was proven to bind to tau aggregated in living mouse brains based on the intensity and life-time of its fluorescent signals. Two other compounds of the same group were radiolabeled with 11C, and were demonstrated to allow both autoradiographic and PET detections of tau lesions in the transgenics.
Conclusion: The present neuroimaging approaches using mouse models of the diseases provide insights into the structural basis of molecular interactions between tau fibrils and exogenous compounds, which would facilitate the development of diagnostic and therapeutic agents for AD and non-AD tauopathies., Alzheimer's Association 2009 International Conference on Alzheimer's Disease},
 title = {In-vivo optical and PET detections of fibrillar tau lesions in a mouse model of tauopathies},
 year = {2009}
}