轻度认知障碍中血清miRNA29与脑磁共振DTI相关性及分子机制

轻度认知障碍(MCI)是正常老化和痴呆的过渡阶段，多数进展为阿尔茨海默病(AD)，目前采用脑脊液淀粉样蛋白Aβ检测以支持诊断，但有创伤性且在疾病晚期才出现异常，尚无敏感特异的诊断标志物。我们的前期工作基于Aβ病理学说，发现miRNA29降解BACE1-mRNA减少Aβ的生成。而Aβ对MCI相关的海马、楔前叶/后扣带回(PC/PCC)神经环路的微结构损伤可采用磁共振弥散张量成像(DTI)早期发现。我们将利用本课题组建立的450例脑磁共振数据库(MCI和AD以及从MCI进展为AD的患者)、血标本及改进的DTI分析方法(BS脑区水平可视化微结构损伤和白质骨架分析)，开展以下研究：1. 探讨海马-PC/PCC神经环路的失协调可能是MCI中以记忆损害为主的神经认知障碍的发生机制；2. 阐明血清miRNA29与DTI的相关性在MCI诊断中的分子机制及预测向AD转化的风险，为AD的预警和治疗提供新思路。

Mild cognitive impairment (MCI) is the transitional state between normal aging and Alzheimer's disease (AD), and most of them will progress to AD. Currently, amyloid Aβ in cerebrospinal fluid was used to support the diagnosis,which is an invasive method and only change in the later stage of disease. There is no sensitive and specific diagnostic biomarkers so far. Based on Aβ pathogenic theory, we found that miRNA29 degradate BACE1-mRNA to reduce Aβ formation. And the microstructure damage of hippocampus, precuneus/posterior cingulate gyrus (PC/PCC) neural circuits due to Aβ in MCI can be early detected by magnetic resonance diffusion tensor imaging (DTI). We will use our brain magnetic resonance database with 450 cases (patients with MCI、AD and MCI who progressed to AD), blood specimen and improved analysis method of DTI (visualization microstructure damage based on cerebral area by BS and white matter skeleton analysis) to do the following study: 1. To discuss whether the discoordination of the hippocampus-PC/PCC neural circuits is the pathogenesis of memory impairment that mainly performed in neural cognitive disorders in MCI. 2. To clarify the molecular mechanism of the correlation of miRNA29 and DTI in the diagnosis of MCI and to predict the risk of AD progression. Results from this project will provide new strategies for the early diagnosis and early warning of AD.