qPMCA技术定量研究血浆错误折叠蛋白质对阿尔茨海默病早期诊断的作用

项目名称： qPMCA技术定量研究血浆错误折叠蛋白质对阿尔茨海默病早期诊断的作用

项目编号： No.81200994

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 陈柏安

作者单位： 首都医科大学

项目金额： 23万元

中文摘要： 血浆β-淀粉样蛋白（Aβ）浓度在阿尔茨海默病（AD）患者和健康人群之间无显著差异，与AD疾病进程及痴呆程度也无显著关联,因此过去基于血浆Aβ作为AD生物标记物的研究面临瓶颈。近期研究提示错误折叠的Aβ（Aβ晶种）可作为AD潜在生物标记物，然而未见相关技术能定量研究Aβ晶种。为了阐明Aβ晶种作为潜在生物标记物对AD早期诊断的作用，本项目拟以APP23转基因小鼠为AD模型，利用我们近期在Nature Methods报道的定量蛋白质错误折叠循环扩增（qPMCA）技术原理测定小鼠不同年龄段血浆Aβ晶种浓度和活力，观察二者的动态规律，比较二者在APP23转基因小鼠和野生型小鼠之间的差异，分析二者与小鼠大脑β淀粉样变性的关联，从实验水平探索血浆Aβ晶种作为AD生物标记物的可能性，为临床利用血浆Aβ晶种作为生物标记物进行AD早期诊断提供理论依据和新技术。本项目对AD早期诊断具有重要的理论意义与应用价值。

中文关键词： qPMCA；Aβ晶种；阿尔茨海默病；生物标记物；

英文摘要： The majority of reports have not detected statistically significant differences of plasma Amyloid-β protein (Aβ) levels in between patients with Alzheimer' s disease (AD) and healthy control subjects. Plasma Aβ levels show no apparent correlation with AD progression and degree of dementia. Thus the plasma Aβ's utility as a biomarker for AD is less compelling. Recent studies suggest the misfolded Aβ (Aβ seeds) could be potent biomarker for AD, however, no techniques have been reported for quantification of Aβ seeds. In order to elucidate the role of Aβ seeds as potent biomarker for early diagnosis of AD, we selected the APP23 transgenic mice for AD model in this project. We then estimated the plasma Aβ seeds level and seeding activity at different ages of mice by using the principle of quantitative protein misfolding cyclic amplification (qPMCA) technology we recently reported in the Nature Methods. We then observed the dynamics of plasma Aβ seeds level and seeding activity in mice. Compared the differences of plasma Aβ seeds level and seeding activity between APP23 transgenic mice and nontransgenic wild type mice. And then analyzed the correlation of plasma Aβ seeds level and seeding activity with cerebral β-amyloidosis. We experimentally explored the possibility of plasma Aβ seeds as AD biomarker. Then we provi

英文关键词： qPMCA；Aβ seeds；Alzheimer's disease；biomarker；