突触丢失和突触可塑性蛋白损伤与Alzheimer病(AD)早期认知障碍最为密切，且发生在老年斑(SP)形成前，而突触可塑性蛋白标志物PSD-95棕榈酰化与AD及衰老的发生和发展是近年刚被关注的热点且研究尚不多见。我们既往研究发现，广泛用于治疗中枢和周围神经损伤的脑苷肌肽(CEGI)具有多靶点改善APP/PS1转基因AD小鼠认知损伤并减少SP生成,更重要的是，我们前期实验发现作用于棕榈酰化的工具药NtBuHA显著减少SP生成。但是，CEGI是否能通过调控蛋白棕榈酰化来影响SP生成，尚不清楚，本项目拟以此为契机，利用尸检人脑组织、APP/PS1转基因小鼠和细胞模型，以皮层和海马棕榈酰化PSD-95为切入点，采用行为学、形态学、酰基-生物素交换法和基因芯片，重点探讨：①PSD-95棕榈酰化及与Aβ代谢关联；②CEGI对PSD-95棕榈酰化影响和分子调控，为寻找防治AD新的靶点提供理论依据。

Synaptic loss and synaptic plasticity injury were most closely related to early cognitive impairment in Alzheimer's disease (AD) and occurrs before senile plaques (SP) formed, whereas the symbolic synaptic plastic protein PSD-95 palmitoylation is associated with AD and aging occurrence and development is the focus of attention in recent years and research is still rare. Our previous study found that that Cattle encephalon glycoside and ignotin injection (CEGI), which is widely used in the treatment of central and peripheral nerve injury, has multi-target improvement cognitive impairment of APP/PS1 transgenic AD mice and significantly reduce the SP formed. More importantly, our previous experiments to depalmitoylation tool drug NtBuHA significantly reduced SP production. However, it is not clear whether CEGI can influence the formation of SP by the regulation of protein palmitoylation, and the project intends to use this as an opportunity to use autopsy human brain tissue, APP /PS1 transgenic mice and cell models , palmitoylated PSD-95 in cerebral cortex and hippocampus as the starting point, using behavior, morphological, acyl-biotinyl exchange (ABE) and microarray, focus on: 1. palmitoylation of PSD-95 and its association with Aβ metabolism; 2. the effect of CEGI on palmitoylation of PSD-95 and molecular regulation, in order to provide the theoretical basis for the new target for the prevention and treatment of AD.