阿尔茨海默病（AD）的发病机制尚不明确。甲酰肽受体2（FPR2）是Aβ的功能受体，其不同配体诱导其表现促炎或抑炎的不同作用。我们前期数据表明，FPR2缺失能减少AD小鼠学习记忆损伤、Tau过度磷酸化及星形胶质细胞激活。由此，我们提出FPR2是参与AD发生发展的重要调节分子：一方面，胶质细胞激活诱导FPR2及配体膜联蛋白A1（ANXA1）表达增加，ANXA1促使小胶质细胞吞噬Aβ，抑制胶质细胞释放促炎因子，保护神经元；而另一方面，过量产生的Aβ作用FPR2诱导胶质细胞释放促炎因子，加剧Aβ及磷酸化Tau的沉积，促进AD进程；同时，神经元上的FPR2也参与AD进程。本项目采用转基因小鼠及STZ侧脑室注射建立两种AD模型，通过FPR2基因缺失和配体激活探究FPR2如何参与AD的发生发展；采用原代细胞验证FPR2的作用机制；最后，通过生物信息学等方法，探究Aβ的GPCR类受体对胶质细胞的作用规律。

The pathogenesis of Alzheimer's disease (AD) is not very clear. Formyl peptide receptor 2 (FPR2) is a functional receptor for Aβ, and its different ligands induce different effects in glial cells, proinflammatory effects or anti-inflammatory effects. Our previous data showed that the deficiency of FPR2 could reduce the impairment of learning and memory, Tau hyperphosphorylation and astrocyte activation in AD model mice. Therefore, we propose that FPR2 plays a key role in the development of AD. One hand, the activated glial cells induce increased expression of FPR2 and its ligands, such as annexin A1 (ANXA1), which promotes microglia phagocytosis of Aβ, inhibits proinflammatory cytokines release by glial cells. On the other hand, the other ligand of FPR2, Aβ, overproduces. Aβ induces the massive release of proinflammatory cytokine in glial cells by interacting with FPR2, increases the deposition of Aβ and hyperphosphorylation of Tau, and promotes AD process. At the same time, FPR2 expressed on neurons is also involved in the development of AD. Based on our previous work, two AD mouse model with FPR2 deficiency will be established in here to verify that if FPR2 is involved in the development of AD, and how FPR2 participates in Aβ accumulation and tau hyperphosphorylation. The mechanism of role of FPR2 will be further explored in vitro by using the primary cell culture system. Finally, by bioinformatics and molecular cloning, exploring the law of function of two Aβ GPCR receptors, FPR2 and Chemokine like receptor 1 (CMKLR1), on the glial cells in AD.