Alzheimer's disease (AD) is characterized by memory impairments in its earliest clinical phase. The synaptic loss and dysfunction leading to failures of synaptic networks in AD brain directly cause cognitive deficits of patient. However, it remains unclear whether the synaptic networks in AD brain could be repaired. In this study, we generated functional human induced neural progenitor/stem cells (iNPCs) that had been transplanted into the hippocampus of immunodeficient wild-type and AD mice. The grafted human iNPCs efficiently differentiated into neurons that displayed long-term survival, progressively acquired mature membrane properties, formed graft-host synaptic connections with mouse neurons and functionally integrated into local synaptic circuits, which eventually reinforced and repaired the neural networks of host hippocampus. Consequently, AD mice with human iNPCs exhibited enhanced synaptic plasticity and improved cognitive abilities. Together, our results suggest that restoring synaptic failures by stem cells might provide new directions for the development of novel treatments for human AD.

阿尔茨海默氏病（AD）的特征是在其最早的临床阶段就出现记忆障碍。导致AD脑中突触网络衰竭的突触丧失和功能障碍直接引起患者的认知缺陷。然而，目前尚不清楚是否可以修复AD脑中的突触网络。在这项研究中，我们生成了功能性人类诱导的神经祖细胞/干细胞（iNPC），该细胞已被移植到免疫缺陷野生型和AD小鼠的海马中。移植的人iNPCs有效分化为神经元，这些神经元显示出长期的生存能力，逐渐获得成熟的膜特性，与小鼠神经元形成了移植物-宿主突触的连接并功能性整合到局部突触回路中，最终增强并修复了宿主海马的神经网络。因此，具有人iNPC的AD小鼠表现出增强的突触可塑性和改善的认知能力。在一起，我们的结果表明，通过干细胞恢复突触衰竭可能为开发人类AD的新疗法提供新的方向。