AD的典型病理特征是Aβ沉淀和神经原纤维缠结，至今病因不明。Sema3A是一种轴突导向因子，调控微管和微丝蛋白的重组装。前期研究显示，Sema3A在AD脑内表达上调且与Aβ沉淀和神经原纤维缠结共定位，并且AD受累神经元中的微管系统遭到破坏后会导致神经原纤维缠结的产生，表明Sema3A很可能与AD典型病理的形成有关。而小G蛋白是生物体活性调控的分子开关，具有组织和调控的特异性，在细胞增殖，细胞骨架网络的构成等信号通路中发挥重要的调节作用。Sema3A受体PlexinA2具有小G蛋白作用的结构域，我们还观察到PlexinA2可以与小G蛋白Rac1结合，推测小G蛋白很可能参与调控Sema3A胞内的信号传递。本课题拟从细胞骨架调控蛋白的角度，揭示Sema3A过表达和小G蛋白在AD病理形成中的作用及其相关的蛋白的调节作用。本项目旨在揭示Sema3A在AD病理形成机理中的作用，为AD成因提供新的依据。

Alzheimer's disease (AD) is a neurodegenerative disease, which is characterized by the formation of typical pathological Aβ deposition and neurofibrillary tangles, while up to now its etiology is still elusive. Semaphorin3A (Sema3A), an axon guidance factor, regulats the re-organization of microtubules and actins. Our preliminary findings and related literatures show that Sema3A is up-regulated and co-localized with Aβ deposition and neurofibrillary tangles in AD. Disruption of the microtubule system in the AD infected neurons leads to the formation of neurofibrillary tangles, which suggests that Sema3A probably take a role in the typical AD pathology formation. The small G proteins are molecular switches regulating many important activities in the organism with their location and regulatory specification, such as cytoskeletal signaling pathways, cell proliferation and formation of cytoskeletal architecture. PlexinA2, Sema3A receptor, has a domain that interacts with the G protein. Our preliminary results show that PlexinA2 can be combined with small G proteins Rac1. It is speculated that the small G protein may mediate the intracellular signal of Sema3A. This project reveals the roles of Sema3A over-expression and small G proteins in AD pathology formation and the regulation mechanism and related proteins in this process from the respective of cytoskeletal regulatory proteins. The project aims to provide a new insight in AD pathogenesis and AD clinical diagnosis by revealing the role of Sema3A in AD pathology formation mechanism.