阿尔茨海默病与β-淀粉样蛋白（Aβ）寡聚体损伤突触功能

神经突触具有高度可塑性，突触的形成和重塑是神经元活动依赖性的，是学习记忆、认知功能的基础。包括阿尔茨海默病（AD）在内的多种表现出认知缺陷的神经疾病，均存在突触结构或者功能的异常。AD病程缓慢，临床早期表现为单纯的记忆功能损伤，证据显示此症状是海马突触效能发生微细改变所致。近20年来，大量实验证实β-淀粉样蛋白（Aβ）寡聚体能够弥散到突触间隙，是最早的损害突触完整性和可塑性的因素。多种不同来源的Aβ寡聚体（包括体外合成的，细胞分泌的，AD转基因动物和AD患者脑内的），能够破坏海马脑片或者动物在体的长时程增强效应（Long-term potentiation, LTP），降低器官型培养的海马脑片的树突棘密度，损害啮齿类动物的认知和记忆功能。AD患者皮质中可溶性Aβ（包括寡聚体）的水平与认知功能呈强相关性。而不可溶的淀粉样沉淀可能是作为具有突触毒性的寡聚体的一种储备。

Beta amyloid (Ab) induced synaptic disfunction in Alzheimer's disease

Synapses are highly motile and can undergo remodeling even in the adult nervous system. Synapse remodeling and the formation of new synapses are activity-dependent processes that provide a basis for memory formation. Many neurological disorders accompanied by cognitive deficits exhibit abnormal synaptic function, including Alzheimer＇s disease （AD）. AD is a progressive disorder, in its earliest clinical phase, characteristically produces a remarkably pt/re impairment of memory. Mounting evidence suggests that the subtle alterations of hippocampal synaptic efficacy prior to frank neuronal degeneration are responsible for the syndrome of cognitive deficits. Over the past decade, mounting data established that the diffusible beta amyloid （Ab） oligomers, as the earliest effectors to adversely affect synaptic structure and plasticity, can diffuse into synaptic clefts and confer synaptic dysfunction underlying cognitive and memory impairment. Ab oligorners from different sources （e. g. , synthetic peptides, cell culture-secreted, AD patients or animal model-derived） can disrupt hippocampal Long-term potentiation （LTP） in slices and in vivo and can also impair the memory of a complex learned behavior in rats. The cell-derived or human-derived oligomers also decrease dendritic spine density in organotypic hippocampal slice cuItures. In humans, memory impairment correlates strongly with cortical levels of soluble Ab species, which include oligomers. Whereas large, insoluble deposits might function as reservoirs of the bioactive oligomers.