Molecular mechanisms of altered adult hippocampal neurogenesis in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is the most common cause of dementia globally. AD is a progressive neurodegenerative disorder, eventually manifesting as severe cognitive impairment. Adult hippocampal neurogenesis (AHN) occurs throughout adulthood and plays an important role in hippocampus-dependent learning and memory. The stages of AHN, predominantly comprising the proliferation, differentiation, survival, and maturation of newborn neurons, are affected to varying degrees in AD. However, the exact molecular mechanisms remain to be elucidated. Recent evidence suggests that the molecules involved in AD pathology contribute to the compromised AHN in AD. Notably, various interventions may have common signaling pathways that, once identified, could be harnessed to enhance adult neurogenesis. This in turn could putatively rescue cognitive deficits associated with impaired neurogenesis as observed in animal models of AD. In this manuscript, we review the current knowledge concerning AHN under normal physiological and AD pathological conditions and highlight the possible role of specific molecules in AHN alteration in AD. In addition, we summarize in vivo experiments with emphasis on the effect of the activation of certain key signalings on AHN in AD rodent models. We propose that these signaling targets and corresponding interventions should be considered when developing novel therapies for AD.