阿尔茨海默病中抗Aβ自身抗体的功能及机制研究

项目名称： 阿尔茨海默病中抗Aβ自身抗体的功能及机制研究

项目编号： No.81200987

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： 邓娟

作者单位： 中国人民解放军第三军医大学

项目金额： 23万元

中文摘要： AD患者中抗Aβ自身抗体的水平和功能变化尚不清楚。我们发现：AD患者抗 Aβ自身抗体具有促进神经元Aβ产生的作用；进一步发现AD患者抗Aβ-N端自身抗体通过促进APP的β酶切、抑制α酶切而促进Aβ产生。而健康人群自身抗体主要针对Aβ中段和C端，具有拮抗Aβ聚集和神经毒性的作用。我们提出假说，自身免疫促进AD的发生发展， AD患者的自身抗体水平和Aβ表位发生变化，促进Aβ过度产生。本项目拟检测和比较AD患者和健康对照抗Aβ自身抗体水平及Aβ抗原表位分布，并分析与AD病情（Aβ水平、认知功能等）的相关性；然后从AD患者和健康对照者血液中分离出抗Aβ自身抗体；进一步从离体和在体水平分析针对不同Aβ表位的抗Aβ自身抗体在促进Aβ产生、抑制Aβ聚集和拮抗 Aβ神经毒性的作用，并探讨抗Aβ自身抗体促进Aβ产生的机制。本项目对于揭示自身免疫在 AD发生发展中的作用和机制具有重要科学意义。

中文关键词： 阿尔茨海默病；Aβ自身抗体；淀粉样前体蛋白；；

英文摘要： It is unclear about the level and function of auto-Aβ antibodies.We found the auto-Aβ antibodies in AD patients could promote Aβ production. We also found the auto-Aβ antibodies againt N-terminal in AD patients could promote Aβ production by promoting APP β-secretase cut and inhibiting APPα-secretase cut.The auto-Aβ antibodies in healthy population were mainly against Aβ middle and C-terminal,with the function of inhibiting abeta aggregation and neurotoxicity.Our hypothesis:Autoimmue reactions promote the occurrence and development of AD. The autoantibody levels and Aβ epitopes change in AD patients could promote Aβ overproduction. The project intends to detect and compare levels and Aβ epitope distributions of auto-Aβ antibodies in AD patients and healthy controls, and analysis the correlation with the AD disease( Aβ levels, cognitive function);Auto-Aβ autoantibodies were isolated from the blood of AD patients and healthy controls;Furthermore, we analysis the effect of different Aβ epitopes of auto-Aβ antibodies on the promotion of Aβ production,inhibition of Aβ aggregation and antagonism of Aβ neurotoxicity in vitro and vivo and exploure the mechanism of auto-Aβ antibodies promoting Aβ production.This project has an important scientific significance in revealing the effect and mechanism of autoimmune effect in

英文关键词： Alzheimer's disease；auto-Aβ antibodies；Amyloid protein precursor；；