Human Neural Stem Cells Reinforce Hippocampal Synaptic Network and Rescue Cognitive Deficits in a Mouse Model of Alzheimer's Disease

Abstract

Summary: 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. : Synaptic failures in AD brain directly cause cognitive deficits of patient. Jing and colleagues reported that the functional integration of human peripheral blood-derived neural progenitor cells reinforced the host neural circuity, improved the synaptic plasticity and rescued the cognitive deficits of AD model mice, indicating that restoring synaptic failures might provide new directions for the development of novel treatments for AD. Keywords: Alzheimer's disease, human induced neural progenitor cells, functional integration, synaptic networks, cognitive improvement