阿尔茨海默病（AD），是最常见的一种老年性痴呆，严重损害人脑记忆功能。遗传因素在AD发生过程中起重要作用，以往对ApoE基因如何影响人脑记忆和认知功能的研究较多，而KIBRA基因对人脑记忆功能调控机制尚不清楚。本项目在前期发现KIBRA基因影响正常青年人默认网络、执行控制网络功能与结构的基础上，进一步利用多模态MRI技术系统研究KIBRA和ApoE基因多态性对健康青年人、健康老年人及AD患者脑结构和功能的联合调控机制，重点阐明KIBRA和ApoE基因调控不同人群记忆功能的主效应及交互效应，揭示AD风险基因携带者脑结构损害与功能变化的关系，以及脑结构、功能损害与记忆功能的关系。该研究将有助于明确KIBRA和ApoE基因作为AD遗传风险因素造成记忆功能损害乃至进展为AD的神经机制。有助建立早期识别AD风险人群的影像遗传学指标，进而为AD患者的早期诊断、早期治疗以及相关药物的研发奠定理论基础。

Alzheimer disease (AD) is the most common form of neurodegenerative dementia and progressively causes metabolic and structural changes in the brain. Genetic factors play an important role in the process of AD. Although the effects of APOE gene polymorphism on the memory function of the human brain have been extensively investigated, the modulation mechanisms of KIBRA gene on the memory function remain largely unknown. Based on our previous finding of the modulation effects of the KIBRA gene on the structure and function of the default mode network and executive control network, we further plan to use multi-modality MRI techniques to systematically investigate the modulation mechanisms of the KIBRA and ApoE gene on the structure and function of the brain in young adults, elder subjects and patients with AD. Importantly, we intend to elucidate both the main effects and interactions of these genes on human memory in different groups and we also hope to clarify the relationships between structural and functional impairments, the impairments and the memory function in the AD risk gene carriers. The study may help to determine the neural mechanisms of the KIBRA and ApoE as the main risk genes of AD resulting in memory impairments and facilitating the development of AD. It also help to establish imaging genetic markers that could identify risk population of AD at an early stage. Finally, the study may lay the foundation for the early diagnosis of AD, early treatment, and the development of related drugs.