A STUDY OF CENTRAL CHOLINERGIC SYSTEMS IN DEMEMTIA

痴呆症中枢胆碱能系统的研究

基本信息

批准号：
09670639
负责人：
SHINOTO Hitoshi
金额：
$ 1.86万
依托单位：
CHIBA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

We have developed a method to measure acetylcholinesterase (AChE) activity, a marker of cholinergic neuronal function, in the brain by positron emission tomography (PET). An analog of acetyIcholine, N-methyl-4-piperidyl acetate (MP4A), was labeled with carbon-11, and brain AChE activity was measured quantitatively using [^<11>C]MP4A.A three-compartment model was applied to calculate regional brain AChE activity using metabolite corrected arterial plasma input function. In Alzheimer's disease (n=19), there was a significant reduction (-24%) of AChE activity in the cerebral cortex, amygdala, and hippocampus compared with age-matched normal controls (n=14). There was a significant inverse correlation between cortical AChE activity and severity of dementia in Alzheimer's disease, supporting cholinergic hypothesis of dementia in Alzheimer's disease. No age effect was seen in normal controls (n=23) ranging in age 24 to 89 years. The results suggest that Alzheimer's disease is not an exaggerated form of normal aging. In Parkinson's disease (n=16), AChE activity in the cerebral cortex and thalamus was often reduced, especially in advanced and demented patients. In progressive supranuclear palsy (PSP : n=12), there was a marked reduction of AChE activity in the thalamus, suggesting that there was a preferential loss of cholinergic system in the brainstem. When the thalamic to cerebral cortical AChE actitity ratio was taken for each subject, Parkinson's disease and PSP were separated, suggesting that PET measurement of AChE activity may be useful for differentiating the two similar disorders.

我们开发了一种通过正电子发射断层扫描 (PET) 测量大脑中乙酰胆碱酯酶 (AChE) 活性的方法，乙酰胆碱酯酶 (AChE) 是胆碱能神经元功能的标志。用碳11标记乙酰胆碱的类似物N-甲基-4-哌啶基乙酸酯(MP4A)，并使用[^11C]MP4A定量测量脑AChE活性。应用三室模型计算使用代谢物校正动脉血浆输入函数来检测区域脑 AChE 活性。与年龄匹配的正常对照组 (n=14) 相比，阿尔茨海默病 (n=19) 的大脑皮层、杏仁核和海马体中的 AChE 活性显着降低 (-24%)。皮质 AChE 活性与阿尔茨海默病痴呆的严重程度之间存在显着的负相关，这支持了阿尔茨海默病痴呆的胆碱能假说。在年龄范围为 24 至 89 岁的正常对照 (n=23) 中未发现年龄效应。结果表明，阿尔茨海默病并不是正常衰老的一种夸张形式。在帕金森病 (n=16) 中，大脑皮层和丘脑中的 AChE 活性常常降低，特别是在晚期和痴呆患者中。在进行性核上性麻痹（PSP：n=12）中，丘脑中的 AChE 活性显着降低，表明脑干中的胆碱能系统优先丧失。当计算每个受试者的丘脑与大脑皮质 AChE 活性比率时，帕金森病和 PSP 是分开的，这表明 PET 测量 AChE 活性可能有助于区分两种相似的疾病。