Synapse loss is the strongest correlate for cognitive decline in Alzheimer's disease. The mechanisms underlying synapse loss have been extensively investigated using mouse models expressing genes with human familial Alzheimer's disease mutations. In this review, we summarize how multiphoton in vivo imaging has improved our understanding of synapse loss mechanisms associated with excessive amyloid in the living animal brain. We also discuss evidence obtained from these imaging studies for the role of cell-intrinsic calcium dyshomeostasis and cell-extrinsic activities of microglia, which are the immune cells of the brain, in mediating synapse loss.

突触丧失是阿尔茨海默氏病认知下降的最强相关因素。已经使用表达人类家族性阿尔茨海默氏病突变基因的小鼠模型对突触丧失的基本机制进行了广泛研究。在这篇综述中，我们总结了多光子体内影像学增强了我们对与活体动物大脑中过量淀粉样蛋白相关的突触丢失机制的理解。我们还讨论了从这些影像学研究中获得的证据，证明细胞内钙离子动态平衡和小胶质细胞的细胞外在活性在介导突触丢失中的作用，小胶质细胞是大脑的免疫细胞。