Abstract
The mammalian hippocampal dentate gyrus is a niche for adult neurogenesis from neural stem cells. Newborn neurons integrate into existing neuronal networks, where they play a key role in hippocampal functions, including learning and memory. In the ageing brain, neurogenic capability progressively declines while in parallel increases the risk for developing Alzheimer's disease (AD), the main neurodegenerative disorder associated with memory loss. Numerous studies have investigated whether impaired adult neurogenesis contributes to memory decline in AD. Here, we review the literature on adult hippocampal neurogenesis (AHN) and AD by focusing on both human and mouse model studies. First, we describe key steps of AHN, report recent evidence of this phenomenon in humans, and describe the specific contribution of newborn neurons to memory, as evinced by animal studies. Next, we review articles investigating AHN in AD patients and critically examine the discrepancies among different studies over the last two decades. Also, we summarize researches investigating AHN in AD mouse models, and from these studies, we extrapolate the contribution of molecular factors linking AD-related changes to impaired neurogenesis. Lastly, we examine animal studies that link impaired neurogenesis to specific memory dysfunctions in AD and review treatments that have the potential to rescue memory capacities in AD by stimulating AHN.
Highlights
Human adult neurogenesis, the generation of new neurons from neural stem cells in specific areas of the adult brain, has been at the center of an intense scientific research over the past years
The temporal correlation between reduced adult hippocampal neurogenesis (AHN) and impaired memory has been the rationale for animal studies investigating whether and how hippocampal newborn neurons contribute to memory
This study reported that a reduced number of BrdU+ cells was already evident in the dentate gyrus (DG) of mutant mice before plaque appearance, while pharmacological rescue of neurogenesis did not alter plaque load [43]
Summary
The generation of new neurons from neural stem cells in specific areas of the adult brain, has been at the center of an intense scientific research over the past years. The impact of ageing on altered AHN and the associated cognitive decline has encouraged researchers to investigate the possibility that deficits in AHN are a complicating factor in Alzheimer’s disease (AD), the most frequent form of dementia and memory loss in ageing individuals This possibility has been intensively debated, due to the lack of a clear and homogeneous methodology for the identification of new neurons in human hippocampal tissues. The present paper is aimed at providing a state-ofthe-art review on studies that link AHN to memory in AD, as well as at delineating the questions that in our opinion should be addressed by scientific and clinical research in the near future We review both relevant experimental investigations about adult neurogenesis in AD patients from the last two decades and studies on mouse models of AD. Given the relevance of AHN for memory, we will limit our discussion to the hippocampus only
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