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Comparative In Vitro and In Vivo Quantifications of Pathologic Tau Deposits and Their Association with Neurodegeneration in Tauopathy Mouse Models.
https://repo.qst.go.jp/records/48881
https://repo.qst.go.jp/records/488819b58dd80-e0aa-4425-bef6-7ea00b73cb7c
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2018-03-05 | |||||
| タイトル | ||||||
| タイトル | Comparative In Vitro and In Vivo Quantifications of Pathologic Tau Deposits and Their Association with Neurodegeneration in Tauopathy Mouse Models. | |||||
| 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_6501 | |||||
| 資源タイプ | journal article | |||||
| 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 |
Ni, Ruiqing
× Ni, Ruiqing× Ji, Bin× Ono, Maiko× Sahara, Naruhiko× Ming-Rong, Zhang× Aoki, Ichio× Nordberg, Agneta× Suhara, Tetsuya× Higuchi, Makoto× Ni, Ruiqing× Ji, Bin× Ono, Maiko× Sahara, Naruhiko× Ming-Rong, Zhang× Aoki, Ichio× Suhara, Tetsuya× Higuchi, Makoto |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Fibrillary tau aggregates in Alzheimer's disease (AD) and allied neurodegenerative disorders have been visualized in-vivo by positron emission tomography (PET), while mechanistic links between PET-detectable tau deposits and neurotoxicity remain elusive. Here, we took advantage of transgenic mouse models of tauopathies to evaluate associations between PET and postmortem measures of tau probe binding and their relation to neuronal loss. Methods: PET with a tau probe, 11C-PBB3 (2-((1E,3E)-4-(6-(11C-methylamino)pyridine-3-yl)buta-1,3-dienyl)benzo[d]thiazol-6-ol), and volumetric magnetic resonance imaging (MRI) were performed for rTg4510 and non-transgenic mice. Binding of 11C-PBB3 and its blockade by another tau binding compound, AV-1451 (-(6-fluoropyridine-3-yl)-5H-pyrido[4,3-b]indole), in homogenized brains of tauopathy patients and rTg4510 and PS19 mice were quantified, and PBB3-positive and phosphorylated tau lesions in sectioned brains of these mice were assessed. Results: In-vivo 11C-PBB3 binding to the rTg4510 neocortex/hippocampus was increased relative to controls, and was correlated with local atrophy. In-vitro 11C-PBB3 binding in the neocortex/hippocampus was also well correlated with in-vivo radioligand binding and regional atrophy in the same individual rTg4510 mice. By contrast, in-vitro 11C-PBB3 binding was elevated in the brainstem but not hippocampus of PS19 mice, despite a pronounced loss of neurons in the hippocampus rather than brainstem. Finally, PBB3 and AV-1451 showed similar binding properties between mouse models and tauopathy patients. Conclusion: The present findings support the distinct utilities of 11C-PBB3-PET along with MRI of rTg4510 and PS19 mice for quantitatively pursuing mechanisms connecting PET-detectable and PET-undetectable tau aggregations to neuronal death, which recapitulate two different modes of tau-provoked neurotoxicity. | |||||
| 書誌情報 |
The Journal of Nuclear Medicine 巻 59, 号 6, p. 960-966, 発行日 2018-02 |
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| 出版者 | ||||||
| 出版者 | Society of Nuclear Medicine | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0161-5505 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 29419480 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.2967/jnumed.117.201632 | |||||
