阿尔茨海默病（AD）发生、发展可能与脑血管功能障碍有关，但具体机制尚不明。我们前期研究发现APP/PSN AD转基因小鼠脑血管内皮细胞上anneixn A2的表达下降，给予外源性重组annexin A2（rA2）能改善AD小鼠海马组织上Aβ的沉积并改善认知功能；进一步在人脑微血管内皮细胞（HBMEC）上发现，rA2能保护Aβ引起的内皮细胞损伤并能促进新生血管的形成，而这可能是annexin A2受体及NFκB依赖的。在本课题中，我们拟利用APP/PSN转基因小鼠、培养的人脑微血管内皮细胞、基因转染及RNA干扰等技术，从整体、细胞和分子水平上阐明annexin A2在阿尔茨海默病脑血管功能障碍中的作用及机制。本课题的完成将深入认识脑血管内皮细胞annexin A2在AD发生、发展中的作用，并可从活化annexin A2及其下游信号通路出发，为相关药物用于治疗AD提供新的思路和新的靶点。

The development of Alzheimer's disease (AD) may be associated with the cerebral vascular dysfunction, but the mechanism remains to be further elucidated. Our preliminary data demonstrated thatthe expression of anneixn A2 inbrain endothelial cellswas decreased in the transgenicAPP/PSN AD mice.Recombinant annexin A2 (rA2) improvedhippocampusAβdepositedand cognitive function in the ADmice.rA2 also protectedAβ-induced cell injury and promoted angiogenesisin the cultured HBMEC, which may be associated with annexin A2 receptor and NF κ B dependent. In this project, AD transgenic mice, RNA interference and gene over-expression technology were used to explore therole and mechanism of annexin A2 on the cerebral vascular dysfunction in Alzheimer's disease.From this project, it will help to know the roles of annexin A2 in AD, and then provide a new way to treat AD byactivatingannexin A2 or its downstream pathways.