The neurogenic niche in Alzheimer's disease.

ABSTRACT

Adult hippocampal neurogenesis is the process of generation and functional incorporation of new neurons, formed by adult neural stem cells in the dentate gyrus. Adult hippocampal neurogenesis is highly dependent upon the integration of dynamic external stimuli and is instrumental in the formation of new spatial memories. Adult hippocampal neurogenesis is therefore uniquely sensitive to the summation of neuronal circuit and neuroimmune environments that comprise the neurogenic niche, and has powerful implications in diseases of aging and neurological disorders. This sensitivity underlies the neurogenic niche alterations commonly observed in Alzheimer's disease, the most common form of dementia. This review summarizes Alzheimer's disease associated changes in neuronal network activity, neuroinflammatory processes, and adult neural stem cell fate choice that ultimately result in neurogenic niche dysfunction and impaired adult hippocampal neurogenesis. A more comprehensive understanding of the complex changes mediating neurogenic niche disturbances in Alzheimer's disease will aid development of future therapies targeting adult neurogenesis.