CLU基因多态性对迟发型阿尔茨海默病人脑情景记忆环路调控的MRI研究

项目名称： CLU基因多态性对迟发型阿尔茨海默病人脑情景记忆环路调控的MRI研究

项目编号： No.81501454

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张鹏

作者单位： 天津医科大学

项目金额： 17万元

中文摘要： 迟发型阿尔茨海默病（LOAD）是最常见的痴呆类型，其早期主要的认知功能损害是情景记忆功能障碍。LOAD具有遗传度高且遗传行为复杂的特点。以前，APOE4是唯一确定的与LOAD相关的危险基因。近年来发现CLU基因多态性与LOAD具有相关性，但其调控LOAD情景记忆环路的神经机制仍不明确。因此，本项目在前期发现CLU基因多态性可影响青年健康人海马功能连接的基础上，运用多模态MRI技术，拟对中国汉族人群的LOAD患者和健康老年人为研究对象，结合情景记忆行为学评估，在控制APOE基因型条件下，进一步研究CLU基因多态性对LOAD情景记忆环路脑结构和功能的影响。该研究有助于寻找早期诊断LOAD的生物学标志，为LOAD的治疗提供新的靶点，以延缓疾病的发生及改善患者受损的认知功能。

中文关键词： 簇连蛋白；基因多态性；迟发型阿尔茨海默病；磁共振成像

英文摘要： Late-onset Alzheimer's disease (LOAD) is the most common form of dementia. The earliest cognitive function deficiency of Alzheimer’s　disease is episodic　memory impairment. LOAD is also characteristic of high heritability and complex genetic behavior.　APOE4 has been previously considered as the unique risk gene associated with LOAD. However, in recent years, CLU gene polymorphism has been confirmed to be associated with LOAD. It is not clear that how CLU influences the neural mechanism of the episodic memory circuit. Thus, we will investigate that how CLU polymorphism, regressed as APOE genotype, influences brain structure and function of the episodic memory circuit in Chinese Han LOAD as well as age-and gender-matched healthy elderly individuals, based on our previous findings of the effect of CLU polymorphism on the functional connectivity of the hippocampus in healthy young adults. Our study tends to find the effective biomarkers of early diagnosis and to advance new targets for its therapies, for delaying its occurrence and reliving its symptoms of the impaired cognitive function of LOAD patients.

英文关键词： CLU;gene polymorphism;late-onset Alzheimer's disease;MRI