2型糖尿病患者脑衰老进程的遗传与影像标志物研究

The patients with type 2 diabetes mellitus (T2DM) have a higher prevalence of earlier brain degeneration, cognitive dysfunctions and even dementia when compared to the same-aged normals. However, little is known about the related mechanism. The influence of T2DM associated apolipoprotein E (ApoE) and the tumor necrosis factor-α (TNF-α) gene polymorphism on brain degeneration and cognitive dysfunctions remains unclear. Besides, the genetic and imaging biomarkers are still lacking. Currently, the multimodal MRI with the multivariate pattern analysis methods has been widely used in detecting neuropsychiatric diseases. Its ability of distinguishing groups by finding structural and functional imaging biomarkers at individual level makes it valuable in the T2DM related brain degeneration study and its clinical application. This study is aimed to reveal the genetic and imaging mechanism of T2DM related brain degeneration and prevent the progression of the disease by providing a theoretical evidence to help the early diagnosis and treatment. On the basis of our previous brain microstructure and function studies in T2DM patients, this study would do efforts in revealing how the ApoE and the TNF-α genes polymorphism work on brain degeneration and cognitive dysfunctions in neuroimaging among T2DM patients. The multimodal MRI with multivariate pattern analysis method would be used to observe the imaging markers. The relationship between the cognitive function and the T2DM risk factors and the prediction of the brain degeneration and the cognitive disorders onset age would be investigated.

T2DM患者较同龄段正常人更早出现脑衰老及多种认知障碍甚至痴呆，但其发生机制，如T2DM的风险基因载脂蛋白E(ApoE)及肿瘤坏死因子α(TNF-α)的基因多态性对脑衰老进程的影响尚不清楚，且缺少相关遗传与影像标志物证据。当前多模态MRI与多变量模式分析方法广泛应用于神经精神类疾病，能在个体水平找到区分群组的结构和功能影像学标记，对T2DM患者脑衰老进程的研究具有重要的临床价值。本项目在前期对T2DM患者脑微观结构及功能研究基础上，探索神经影像学层面ApoE基因及TNF-α基因多态性对T2DM患者脑衰老进程的影响，并应用多模态MR及多变量模式分析方法提取T2DM患者的脑影像标志物，探讨其与认知功能及T2DM多种危险因素的相关性并预测T2DM患者更早出现脑衰老及认知功能障碍的高发年龄段，揭示其遗传影像学机制，为早期诊断与治疗以延缓疾病进程提供实验依据。

T2DM患者较同龄段正常人更早出现脑衰老及多种认知障碍甚至痴呆，但其发生机制，如T2DM认知障碍相关易感基因多态性对脑衰老进程的影响尚不清楚，且缺少相关遗传与影像标志物证据。当前多模态MRI与多变量模式分析方法广泛应用于神经精神类疾病，能在个体水平找到区分群组的结构和功能影像学标记，对T2DM患者脑衰老进程的研究具有重要的临床价值。本项目在前期对T2DM患者脑微观结构及功能研究基础上，探索神经影像学T2DM认知障碍相关易感基因多态性对T2DM患者脑衰老进程的影响，并应用多模态MR及多变量模式分析方法提取T2DM患者的脑影像标志物。我们发现T2DM患者认知功能较同年龄段人群有所减低，体现在丘脑、额叶、颞叶等脑区结构与功能发生了异常改变，且与临床指标，包括糖化血红蛋白、血脂等密切相关。另一方面，我们初步发现T2DM患者认知功能障碍的发生与跨膜蛋白106B（TMEM106B）及纤溶酶原激活物，尿激酶（PLAU）基因多态性密切相关。这些发现将有利于我们对T2DM患者认知障碍的发生及发展机制作进一步的研究，为早期诊断与治疗以延缓疾病进程提供实验依据。