脑脊液微净化吸附去除脑实质Aβ可行性研究

项目名称： 脑脊液微净化吸附去除脑实质Aβ可行性研究

项目编号： No.81671073

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 徐丽

作者单位： 大连理工大学

项目金额： 25万元

中文摘要： 以Aβ为靶标的阿尔茨海默病（AD）治疗效果不理想使大家对Aβ是否是AD发生发展的诱导因素提出了质疑，仔细分析发现以Aβ为靶标的AD治疗存在多方面不足，因此需要找到一种副作用小又能有效去除脑实质Aβ的方法。基于最近对脑实质类淋巴系统和脑脊液在脑内物质运输方面的新发现，以及微透析采样技术的优点与缺点，本申请提出微净化去除脑脊液Aβ，进一步去除脑实质Aβ的研究方法。首先制备Aβ纳米抗体，并以此为配基制备吸附剂；再将吸附剂灌注到微透析管路内，制备出Aβ微净化系统；然后将不同类型和浓度的Aβ聚集体注射到不同年龄大鼠脑实质不同部位，借助微净化系统，吸附去除脑脊液Aβ。本研究提供了一种新的脑脊液致病因子去除方法，并为能否通过该方法吸附去除Aβ和把握AD治疗时机提供依据。

中文关键词： 阿尔茨海默病；淀粉样蛋白β；类淋巴系统；脑脊液；微净化

英文摘要： Because drugs targeted to Aβ showed ineffective on treatment of Alzheimer's disease (AD), many peoples question whether Aβ is the inducing factor of AD. Detailed analysis found that there are many deficiencies in the method and procedure of the AD treatment targeted to Aβ. Thus, to solve the problems, a new method is needed to fast remove Aβ in brain parenchyma and the time of the treatment should be re-considered. Based on the new knowledge of glymphatic system and cerebrospinal fluid (CSF) which shows important functions on substance transportation from parenchyma to CSF, and the advantage and disadvantage of microdialysis technique which could obtain research samples in vivo, we provide a new method called micro-purification technique, which might remove Aβ from CSF directly and brain parenchymal indirectly. Simply, Aβ adsorbents are obtained after Aβ nanobodies are synthesized on matrix, micro-purification system is prepared by piping Aβ adsornent into piping system of microdialysis. At last, Aβ is removed through micro-purification system. Our research would provide not only a new method to remove pathogenic agents in CSF, including Aβ, but also the time to treatment AD.

英文关键词： Alzheimer's disease;amyloid beta; glymphatic system ;cerebrospinal fluid;micro-purification