Inhibiting Adult Neurogenesis Ameliorates Synaptic and Cognitive Deficits in Animal Models of Alzheimer’s Disease

Abstract

Adult-born new neurons are associated with a variety of cognitive functions. Previous studies have indicated that adult neurogenesis is disturbed in the brain of Alzheimer's disease (AD) patients and animal models. However, whether and how newborn neurons affect the neuropathology in AD is not clear. Here, we found that genetic or drug induced ablation of adult-born new neurons significantly ameliorated synaptic and cognitive impairments in APP/PS1 and hAPP-J20 mice, two commonly used mouse models of AD. Furthermore, inhibiting adult neurogenesis did not affect the levels of soluble amyloid β (Aβ), the deposition of amyloid plaques, and the proteolytic cleavage of hAPP but increased the activity of hippocampal granule cells. Taken together, our study demonstrates beneficial effects of inhibiting adult neurogenesis on AD pathology, and these effects were caused presumably by improving the activity of granule cells in the dentate gyrus but not by reducing Aβ levels in brains of AD mice.