阿尔茨海默病（AD）是最常见的神经变性病，患者以痴呆为主要表现，生活不能自理，给家庭和社会造成极大负担。高加索人GWAS研究及我们小组前期研究均发现CD2相关蛋白（CD2AP）基因多态性与晚发性AD发病风险有关。在肾小球，CD2AP与肌动蛋白（actin）相互作用，维持足细胞形态。但CD2AP在神经系统的功能研究甚少。最新发现CD2AP减少会加强异常tau对神经元的损伤。异常Tau损伤增加F-actin聚集，影响神经元突触重要组成部分树突棘的功能。后者的形态由F-actin骨架结构维持。综合上述研究结果，我们推测CD2AP对异常Tau损伤起保护作用，且可能通过调节F-actin或突触结构及功能来实现。本研究利用CD2AP过表达或表达下调的细胞模型及突变Tau的AD小鼠模型（Tg4510），观察CD2AP在AD Tau损伤机制中对神经元的保护作用及机制。上述研究可为AD治疗提供新靶点。

Alzheimer’s disease (AD) is the most common neurodegenerative disease. AD patients are characterized by dementia and should be taken care of in the late stage of the disease, which is a huge burden to the families and the society. Recent Genome wide association studies (GWAS) and investigation in our institute indicated the single nucleotide polymorphisms (SNP) of CD2 associated protein (CD2AP) gene modulated the AD risk. In renal glomerulus, CD2AP interacts with actin, maintaining the structure of podocyte. But its function in central nervous system is not clear. Latest research indicated low level of CD2AP enhanced the Tau neurotoxicity to neuron. Tau neurotoxicity enhanced the abnormal accumulation of F-actin and influenced the function of dendritic spine. Dendritic spine is the important part of synapse and its structure is supported by F-actin. So, we speculated that CD2AP played a protective role in Tau induced neurotoxicity, which might be caused by regulation of F-actin structure or synaptic function. Here we will prepare the AD cell model overexpression or inhibited expression of CD2AP, together with the AD mice model (Tg4510), to explore the probable role of CD2AP in Tau neurotoxicity in AD pathogenesis. This investigation will be helpful to find the therapy target of AD.