阿尔茨海默病关键病理蛋白及其功能机制研究

阿尔茨海默病（Alzheimer's disease，AD）是严重危害老年人身心健康的疾病之一，尚无有效延缓或逆转疾病进程的干预和治疗手段。国内外研究证实，AD发病机制复杂，且病程进展中伴随多种异常生物学功能的动态改变。本团队前期在国人AD临床队列中发现多种与AD发病相关的遗传和体液标志物，涉及Aβ代谢、神经炎症、线粒体功能和脂质代谢等生物学过程。这些标志物能够在AD患者无症状期做出早期诊断，推测它们参与AD重要的病理过程，但其是否为关键病理蛋白以及发挥何种作用，尚未明确。本研究拟基于前期建立的AD不同临床阶段的研究队列，利用蛋白组学和生物信息学方法，在前期研究结果的基础上，发现和验证与AD发病机制密切相关的病理蛋白，通过细胞模型和动物模型深入探索病理蛋白的生物学功能尤其是关键致病和调控机制，探寻潜在干预途径，为开发AD创新药物奠定理论基础。

Alzheimer's disease (AD) is one of the diseases that seriously harm the physical and mental health of the elderly, and there is no effective intervention and treatment means to delay or reverse the disease. Studies have confirmed that the pathogenesis of AD is complex, and the progression of the disease is accompanied by dynamic changes in various abnormal biological pathways. In the past two decades, our team found a variety of genetic and humoral markers related to the pathogenesis of AD in the clinical cohort of Chinese people, which are involved in the biological processes such as Aβ metabolism, neuroinflammation, mitochondrial function and lipid metabolism. These markers can be used to make early diagnosis in patients with AD at the asymptomatic stage, and we speculated that they are involved in the important pathological process of AD. However, whether they are key pathological proteins and what mechanisms they play have not been clear. Based on our previous findings, this study intends to discover and verify key pathological proteins related to the pathogenesis of AD by using proteomics and bioinformatics methods. Furthermore, the biological functions and pathogenic mechanisms of pathological proteins will be explored in vitro and in vivo, to help to find the potential intervention. Our work will lay a theoretical foundation for the development of AD innovative drugs.