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アセチルコリンアナログを用いた中枢アセチルコリンエステラーゼ活性のin vivo測定
https://repo.qst.go.jp/records/44413
https://repo.qst.go.jp/records/44413e88d380b-836b-4973-8cd6-66ac0442bf09
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2006-07-06 | |||||
| タイトル | ||||||
| タイトル | アセチルコリンアナログを用いた中枢アセチルコリンエステラーゼ活性のin vivo測定 | |||||
| 言語 | ||||||
| 言語 | jpn | |||||
| 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 |
長塚, 伸一郎
× 長塚, 伸一郎× 難波, 宏樹× 篠遠, 仁× 伊豫, 雅臣× 福士, 清× 入江, 俊章× 長塚 伸一郎× 難波 宏樹× 篠遠 仁× 福士 清× 入江 俊章 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Reduction of central acetylcholinesterase (AChE) activity, that is accompanying with degeneration of cholinergic nerve system, has been known to be the most consistent neurochemical change seen in the brain of demented patients with Alzheimer's disease(AD) or other neurological disorders. In order to detect central cholinergic deficits, we have selected AChE as the target enzyme and have synthesized several lipophilic acetylcholine analogs that are metabolically trapped in the brain. Of the analogs, N-[11C]methylpiperidyl-4-acetate (MP4A) showing high specificity against human cerebral AChE was selected and applied to positron emission tomography (PET). Kinetic analysis based on the arterial input function and 3-compartment model gave tracer uptake, washout and metabolic rate constants. Tracer uptake rate was almost identical to regional cerebral blood flow (rCBF) rate. Metabolic rates in regions with relatively low AChE activity (cerebral cortex, hippocampus and htalamus) correlated well with ratio of AChE activity obtained from brain necropsy samples. While the values in high AChE regions such as cerebellum and striatum gave larger variance because of flow limitation of radioactivity distribution. In normal subjects, age-related changes in cortical AChE activity could not be detected from 24 to 89 years old, despite the significant age-related reduction of cortical rCBF. In ppatients with early AD, significant reduction of cortical AChE activity could be detected. The reduction of AChE activity was widespread throughout the whole cortical regions while cortical rCBF was reduced only in the patietotemporal cortex. This method also clarified the significant reductions of cortical AChE activity in patiens with Parkinson's disease (PD) and thalamic AChE activity in patients with progressive supranuclear palsy (PSP). THese results suggest degeneration of cholinergic projection from the basal forebrain to the cerebral cortex in PD and that of the projection from the brainstem to the thalamus in PSP. In conclusion, non-invasive measurement of central AChE activity was achieved by PET using MP4A. The method is promising for neurochemical analysis, early diagnosis and/or therapeutic evaluation for dementing disorders. |
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| 書誌情報 |
脳のイメージング(SciMed Nneuroscience Series ; 3) p. 69-80, 発行日 1999 |
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| 出版者 | ||||||
| 出版者 | サイメッド・パブリケーションズ | |||||
| ISBN | ||||||
| 識別子タイプ | ISBN | |||||
| 関連識別子 | 4-9159-3722 | |||||
