异常的突触可塑性在阿尔茨海默病（Alzheimer's disease，AD）的病理进程中发挥重要作用。目前有研究发现突触可塑性的异常早于 Aβ的聚集、神经纤维的缠结和神经元缺失这些病理过程，在AD中的价值已引起关注。本课题组经过前期研究的积累，发现基于“虚损-浊毒”中药复方有良好的抗AD、减轻APP/PS1双转基因小鼠Aβ毒性损害、抑制γ分泌酶活性及调节相关组分的作用，据此进一步提出“基于‘虚损-浊毒’中药复方抗痴呆作用与调节异常的突触可塑性有关”的假说，为验证该假说，本研究采用PScDKO小鼠AD模型及相应的原代神经细胞模型为评价载体，以PS/γ分泌酶为切入点，Neurexin1及相互作用蛋白为主要靶点，采用神经分子生物学研究技术和手段，探索中药复方抗AD、调节突触可塑性的分子机制，为抗AD药物研究寻找新作用靶点，也为中医药研究AD提供参考和借鉴。

Abnormal synaptic plasticity plays an important role in the pathological courses of Alzheimer’s disease(AD).Nowdays,studies have found that abnormal synaptic plasticity arise earlier than plaques,neurofibrillary tangles and neuronal loss ,which had generally received attention. Building on that earlier research of our group,we have discovered that the Chinese herbal medicine based on the theory “viscera-stasis toxin” had good effect in anti dementia,anti Aβ toxicities of of APP/PS1 double transgenic mice with AD,inhibit the activity of gamma-secretase. According to the preliminary experiment results,we pointed out the hypothesis that “the effect of anti dementia of the Chinese herbal medicine based on the theory “viscera-stasis toxin”was related to regulate the abnormal synaptic plasticity”. To test this hypothesis,this study use molecular biological technology, take PScDKO mice model with AD as appraisal carrier,PS/γsecretase as main target sites,start with Neurexin1 and interacting protein to explore the molecular mechanism of anti dementia, regulate the abnormal synaptic plasticity of the Chinese herbal compound, to further offer a target for new drugs and provid a reference for future development.