β-淀粉样蛋白清除对AD脑内失营养性神经突起的影响

项目名称： β-淀粉样蛋白清除对AD脑内失营养性神经突起的影响

项目编号： No.81200837

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： 蔡艳

作者单位： 中南大学

项目金额： 24万元

中文摘要： 失营养性神经突起（DN）是形成阿尔茨海默病（AD）致密型老年斑的重要组分，研究发现DN数量与AD认知障碍的严重程度呈正相关。AD免疫治疗是清除β-淀粉样蛋白(Aβ)的常用方法，被认为可有效降低AD动物及人脑内淀粉斑的沉积，改善动物的行为学，但不能有效遏制AD患者认知功能的进行性地下降。本课题组前期发现DN出现早于Aβ在胞外的沉积，提示DN的形成可能不完全由Aβ毒性作用所致，单纯清除Aβ不能完全阻止DN的形成与进一步发展。为验证这一假说，本项目采用生物化学和组织病理学方法,在淀粉斑形成前、后两个不同时期分别对APP/PS1双转基因小鼠进行AD主动及被动免疫处理, 观察Aβ清除对小鼠脑内DN的影响,探明AD脑内DN与Aβ的关系，为进一步完善AD理论及治疗提供新思路。

中文关键词： 阿尔兹海默病；淀粉蛋白病变；脑老化；神经轴突病变；

英文摘要： Dystrophic neurites （DNs）are the main components of the compact plaques in Alzheimer's disease. There is positive relationship between DNs and cognitive deficit. It is shown that the numbers of DNs are positively correlated to the cognition deficit in AD. β-amyloid(Aβ) clearance with the immunotherapy is considered to reduce amyloid burden in both of AD animals and patients brains effectively and improve animal behaviors. But the progressively cognition decline was not be rescued. Our previous study demonstrated that DNs appear before the formation of amyloid plaques, which indicate that formation of DNs may not be caused completely by toxicity of Aβ, so that simple removement Aβ can't reverse or prevent formation and development of DNs. In order to verify the hypothesis, the active and passive immunotherapy are used to explore the influence of Aβ clearance on DNs in the brain of APP/PS1 mice before and after the formation of amyloid with the methods of biochemistry and histopathology, the relationship between DNs and Aβ deposition will be investigated which will provide new ideas for theory and treatment of AD.

英文关键词： Alzheimer’s disease；amyloid pathogenesis；brain aging；pathology；