Bai Feng, Liao Wei, Yue Chunxian, Pu Mengjia, Shi Yongmei, Yu Hui, Yuan Yonggui, Geng Leiyu, Zhang Zhijun
Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, The Institute of Neuropsychiatry of Southeast University, Nanjing, 210009, China.
Center for Cognition and Brain Disorders, Hangzhou Normal University, Hangzhou, 310015, China.
Brain Struct Funct. 2016 Jan;221(1):433-46. doi: 10.1007/s00429-014-0916-4. Epub 2014 Oct 25.
The tau hypothesis has been raised with regard to the pathophysiology of Alzheimer's disease (AD). Mild cognitive impairment (MCI) is associated with a high risk for developing AD. However, no study has directly examined the brain topological alterations based on combined effects of tau protein pathway genes in MCI population. Forty-three patients with MCI and 30 healthy controls underwent resting-state functional magnetic resonance imaging (fMRI) in Chinese Han, and a tau protein pathway-based imaging approaches (7 candidate genes: 17 SNPs) were used to investigate changes in the topological organisation of brain activation associated with MCI. Impaired regional activation is related to tau protein pathway genes (5/7 candidate genes) in patients with MCI and likely in topologically convergent and divergent functional alterations patterns associated with genes, and combined effects of tau protein pathway genes disrupt the topological architecture of cortico-cerebellar loops. The associations between the loops and behaviours further suggest that tau protein pathway genes do play a significant role in non-episodic memory impairment. Tau pathway-based imaging approaches might strengthen the credibility in imaging genetic associations and generate pathway frameworks that might provide powerful new insights into the neural mechanisms that underlie MCI.
关于阿尔茨海默病（AD）的病理生理学，已经提出了tau假说。轻度认知障碍（MCI）与发生AD的高风险相关。然而，尚无研究基于tau蛋白通路基因的联合效应直接检测MCI人群的脑拓扑改变。43例MCI患者和30名健康对照者接受了静息态功能磁共振成像（fMRI）检查，研究采用基于tau蛋白通路的成像方法（7个候选基因：17个单核苷酸多态性）来探究与MCI相关的脑激活拓扑组织变化。区域激活受损与MCI患者的tau蛋白通路基因（5/7个候选基因）有关，可能与基因相关的拓扑汇聚和发散功能改变模式有关，并且tau蛋白通路基因的联合效应破坏了皮质-小脑环路的拓扑结构。这些环路与行为之间的关联进一步表明，tau蛋白通路基因在非情景记忆障碍中确实起着重要作用。基于tau通路的成像方法可能会增强成像遗传关联的可信度，并生成通路框架，这可能为MCI潜在的神经机制提供强大的新见解。
