磷脂酰肌醇结合网格蛋白装配蛋白(PICALM)基因是新发现的、与迟发型阿尔茨海默病(LOAD)相关的易感基因。最新的META分析表明，在中国人群中PICALM rs3851179变体与AD之间存在显著相关性，且这种相关性不受载脂蛋白Eε4的影响。目前，关于PICALM基因型与AD发生率关系的研究尚少，且PICALM基因与AD认知与执行功能损伤是否有关联以及关联机制未明。研究表明PICALM基因与某些MR神经影像特征相关，预试验表明LOAD患者存在脑功能网络改变。因此我们假设PICALM基因通过影响脑组织结构、功能环路和脑代谢，从而影响AD进展。本项目拟采用脑结构性MR成像、脑功能网络分析及PET成像，研究LOAD患者的脑结构、功能网络及脑代谢改变，及其与PICALM基因的相关性，以探讨PICALM基因在LOAD中的分子和遗传神经机制，以辅助制定AD风险的个体化防治措施。

Phosphatidylinositolbinding clathrin assembly protein (PICALM) was a sensitive gene which was recently discovered genetic risk factors for late-onset Alzheimer’s disease (LOAD). The latest META analysis revealed the significant correlation between PICALM gene rs3851179 and AD occurrence rate, which was not affected by apolipoprotein E ε4. So far, there were few studies about correlation between PICALM gene rs3851179 and AD incidence, and between PICALM gene and AD relevant symptoms (cognitive and executive disorder) either. Moreover, the mechanism underlying the correlation was still an enigma. Researchers demonstrated that PICALM gene was pertaining to influence some neuroimaging traits which would provide important confirmation of a role for the genetic variants and the pilot study showed there were brain functional networks changes in LOAD patients. Therefore, we put forward a hypothesis that PICALM gene would influence biological processes underlying development of AD, might by some neuroimaging traits changes, containing brain structure measurements, functional circuit, as well as brain metabolism changes. This program focuses on the changes of brain structure, brain functional networks and brain metabolism in LOAD patients and the correlations between these changes and PICALM gene, using structure MRI, resting-state functional MRI and PET respectively, to explore the molecular and genetic mechanisms through which the PICALM gene might be acting in LOAD patients, and to achieve early prevent and make personal prevent plan for AD risk.