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In-vivo optical and PET detections of fibrillar tau lesions in a mouse model of tauopathies
https://repo.qst.go.jp/records/69813
https://repo.qst.go.jp/records/69813cc524a16-3286-4d2c-b23e-185ebf35bb79
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2009-07-24 | |||||
| タイトル | ||||||
| タイトル | In-vivo optical and PET detections of fibrillar tau lesions in a mouse model of tauopathies | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Maruyama, Masahiro
× Maruyama, Masahiro× Maeda, Jun× Ki, Hin× Zhang, Ming-Rong× Okauchi, Takashi× Ono, Maiko× Hattori, Satoko× Q., Trojanowski John× M.-Y., Lee Virginia× Fukumura, Toshimitsu× Higuchi, Makoto× Suhara, Tetsuya× 丸山 将浩× 前田 純× 季 斌× 張 明栄× 岡内 隆× 小野 麻衣子× 服部 聡子× 福村 利光× 樋口 真人× 須原 哲也 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 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. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Alzheimer's Association 2009 International Conference on Alzheimer's Disease | |||||
| 発表年月日 | ||||||
| 日付 | 2009-07-16 | |||||
| 日付タイプ | Issued | |||||
