阿尔茨海默病(AD)是最常见的神经变性病，其病因和发病机制仍不明确。CD2相关蛋白(CD2AP)是AD的危险因素，但CD2AP增加AD发病风险的机制至今不明。我们前期研究表明CD2AP可影响N-甲基-D-天冬氨酸受体(NMDAR)信号通路中突触相关蛋白的表达，参与了突触可塑性的调控作用，而NMDA受体是突触可塑性的关键分子，提示CD2AP可能通过调节NMDAR的活性影响突触可塑性，引起认知功能损害，但其具体机制尚不清楚。本项目基于前期基础构建CD2AP神经元条件性敲除 PS1/APP 5xFAD小鼠模型，研究CD2AP对该小鼠学习记忆和海马长时程增强的影响，并结合上述转基因小鼠来源的海马神经元细胞模型，深入探讨CD2AP调节突触可塑性的分子机制。本研究将有助于阐明 CD2AP调节突触可塑性在AD发病机制中的重要作用。

Alzheimer’s disease (AD) is the most common neurodegenerative disease with unknown etiology and pathogenesis. CD2-associated protein (CD2AP) is an important risk factor of AD. But the mechanism of CD2AP for increasing the susceptibility of AD is unclear so far. Our previous study had found that CD2AP regulated the expression of synaptic related protein in N-methyl-d-aspartate receptor (NMDAR) signaling pathway, and involved in the regulation of synaptic plasticity, and NMDAR is the key molecules for synaptic plasticity, which speculates that CD2AP may regulate the activity of synaptic plasticity through NMDAR, but the mechanisms have not been elucidated. This study we will build a PS1/APP 5xFAD mice model of CD2AP conditional knock out, and then observe the affection on learning, memory and hippocampal long-term potentiation of the mice model, and also establish the cell model of hippocampal neuron which from those transgenic mice, and to investigate the molecular mechanism of CD2AP in regulating synaptic plasticity. This study will elucidate the molecular mechanism of CD2AP on regulation of NMDAR function, and contribute to clarify CD2AP how to regulate the synaptic plasticity which is an important role in the pathogenesis of AD.