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In vivo positron emission tomographic imaging of glial responses to amyloid-beta and tau pathologies in mouse models of Alzheimer's disease and related disorders
https://repo.qst.go.jp/records/46044
https://repo.qst.go.jp/records/46044ef67c73f-f22c-4bb7-a42c-ca9bb7659323
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2011-05-23 | |||||
| タイトル | ||||||
| タイトル | In vivo positron emission tomographic imaging of glial responses to amyloid-beta and tau pathologies in mouse models of Alzheimer's disease and related disorders | |||||
| 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 |
Maeda, Jun
× Maeda, Jun× Zhang, Ming-Rong× Okauchi, Takashi× Ki, Hin× Ono, Maiko× Hattori, Satoko× Kumata, Katsushi× Iwata, Nobuhisa× Saido, Takaomi× Q., Trojanowski John× M.-Y., Lee Virginia× Staufenbiel, Matthias× Mori, Hiroshi× Fukumura, Toshimitsu× Suhara, Tetsuya× Higuchi, Makoto× et.al× 前田 純× 張 明栄× 岡内 隆× 季 斌× 小野 麻衣子× 服部 聡子× 熊田 勝志× 森 啓× 福村 利光× 須原 哲也× 樋口 真人 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Core pathologies of Alzheimer's disease (AD) are aggregated amyloid-beta peptides (Abeta) and tau, and the latter is also characteristic of diverse neurodegenerative tauopathies. These amyloid lesions provoke microglial activation, and recent neuroimaging technologies have enabled visualization of this response in living brains using radioligands for the peripheral benzodiazepine receptor also known as the 18-kDa translocator protein (TSPO). Here we elucidated contributions of Abeta and tau deposits to in vivo TSPO signals in pursuit of mechanistic and diagnostic significance of TSPO imaging in AD and other tauopathies. A new antibody to human TSPO revealed induction of TSPO-positive microgliosis by tau fibrils in tauopathy brains. Emergence of TSPO signals prior to occurrence of brain atrophy and thioflavin-S-positive tau amyloidosis was also demonstrated in living mice transgenic for mutant tau by positron emission tomography (PET) with two classes of TSPO radioligands, [11C]AC-5216 and [18F]fluoroethoxy-DAA1106. Meanwhile, only modest TSPO elevation was observed in aged mice modeling Abeta plaque deposition, despite the notably enhanced in vivo binding of amyloid radiotracer, [11C]Pittsburgh Compound-B, to plaques. In these animals, [11C]AC-5216 yielded better TSPO contrasts than [18F]fluoroethoxy-DAA1106, supporting the possibility of capturing early neurotoxicity with high-performance TSPO probes. Furthermore, an additional line of mice modeling intraneuronal Abeta accumulation displayed elevated TSPO signals following noticeable neuronal loss, unlike TSPO upregulation heralding massive neuronal death in tauopathy model mice. Our data corroborate the utility of TSPO-PET imaging as a biomarker for tau-triggered toxicity, and as a complement to amyloid scans for diagnostic assessment of tauopathies with and without Abeta pathologies. | |||||
| 書誌情報 |
The Journal of Neuroscience 巻 31, 号 12, p. 4720-4730, 発行日 2011-03 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0270-6474 | |||||
