GPR40是发现较晚的G蛋白偶联受体亚型，能被多不饱和脂肪酸激活，促进环磷腺苷效应元件结合蛋白（CREB)磷酸化,提高BDNF表达,促进神经生长。在阿尔茨海默症（AD）患者脑内，磷酸化的CREB（p-CREB）水平较低，由CREB介导的信号通路被抑制。我们前期工作显示：GPR40受体激动剂GW9508可以改善Aβ1-42 AD模型小鼠的记忆认知障碍，其机制可能与提高海马区p-CREB和神经营养因子（BDNF、NGF、NT-3、NT-4）的表达相关，该作用可被GPR40受体拮抗剂GW1100所阻断。这提示GPR40受体可能作为AD治疗新靶点。本研究在此基础上围绕GPR40受体，采用APP/PS1双转基因AD小鼠,从体内外以及PUFA-GPR40-CREB和PLC/IP3两条通路，开展多层次的系统研究，为阐明GPR40在AD发病和治疗中的作用和机制，寻找AD治疗药物新靶点提供实验依据和思路。

GPR40 is a member of G protein–coupled receptors (GPCR) which is lately found. It could be activated by polyunsaturated fatty acids (PUFA) and enhance the phosphorylation of cyclic AMP response element binding protein (CREB), improve the expression of brain derived neurotrophic factor (BDNF) and promote the growth of neuron. The expression of phosphorylation CREB (p-CREB) in the brains of Alzheimer's disease (AD) patients was very low and the signal pathway mediated by CREB is suppressed. The previous research work of our group has demonstrated that GPR40 receptor agonist GW9508 could significantly ameliorated cognitive performance in Aβ1-42-induced AD model mice and its mechanism may be related to that the activation of GPR40 receptor could promote the phosphorylation of CREB and significantly increase the expression of neurotropic factors including brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and neurotrohin-4 (NT-4) in mouse hippocampal neurons which contribute to neurogensis. The function could be significantly reversed by GPR40 receptor antagonist GW1100, this suggested that GPR40 is a potential drug target for the treatment and prevention of AD. Based on the previous study, in the present research, Hierarchical study was carried out using APP/PS1 transgenic mouse to study the PUFA-GPR40-CREB and PLC/IP3 pathways and clarify the role and mechanism of GPR40 on AD in pathogenesis and therapy which provide experimental evidence and ideas in search of the therapeutic drug target of AD.