携带高危基因APOEε4的糖尿病患者进展为AD的脑影像机制

阿尔茨海默病（Alzheimer's disease，AD）是一种起病隐匿的渐进性发展的神经系统退行性疾病，难以早期识别。而2型糖尿病是AD重要的风险因素，也是可控因素。载脂蛋白E（Apolipoprotein E，APOE）ε4等位基因是AD最重要的风险基因，同时APOEε4等位基因也可以改变糖尿病患者患AD的风险。糖尿病和APOEε4 之间具有协同的联合效应，但是目前针对APOEε4基因和2型糖尿病双重风险因素在AD病理发生发展过程的研究不足，潜在的作用机制仍不明确。因此，本研究拟综合多模态神经影像学技术，深入挖掘反映携带APOEε4基因的2型糖尿病患者进展为AD的关键标记物，阐明不同APOEε4基因型对2型糖尿病与AD关系的调节机制，探索基因-疾病-脑的关联机制，为揭示AD发病机制和病理进展模式提供新的启发，对AD的新药研发亦有重要的指导意义。

Alzheimer's disease (AD) is a progressive neurodegenerative disease with insidious onset that is difficult to identify early. Type 2 diabetes is an important risk factor for AD and a controllable factor. The apolipoprotein E (APOE) ε4 allele is the most important risk gene for AD, and the APOE ε4 allele can also change the risk of AD in diabetic patients. There is a synergistic association between diabetes and APOE ε4, but the study on APOE ε4 gene and the dual risk factors of type 2 diabetes in the pathogenesis and development of AD is still not clear. Therefore, this study intends to integrate the multi-modal neuroimaging techniques to explore the key marker of APOE ε4 gene in patients with type 2 diabetes, elucidate the regulatory mechanism of different APOE ε4 genotypes on the relationship between type 2 diabetes and AD, and explore the mechanism of gene-disease-brain association. It provides new inspirations to reveal the pathogenesis and pathologic progression pattern of AD, and also has important guiding significance to the new drug development of AD.