Soluble amyloid precursor protein-α rescues age-linked decline in neural progenitor cell proliferation

Neurobiol Aging. 2013 Oct;34(10):2431-40. doi: 10.1016/j.neurobiolaging.2013.04.016. Epub 2013 May 14.


Neurogenesis is thought to play a role in cognitive function and hippocampal plasticity. Previous studies suggest that neurogenesis declines with aging. However, the onset and mechanism of declined neurogenesis are not fully elucidated. Here we show that the major decline in neurogenesis takes place during adulthood, before aging. Decline in neurogenesis takes place in the subgranular layer of the dentate gyrus and in the subventricular zone, and is primarily due to a reduced number of fast-proliferating neural progenitor cells. Importantly, this decline can be rescued by intraventricular injection of recombinant soluble amyloid precursor protein (sAPPα), which regulates neural progenitor cell proliferation in the adult brain. The counterpart, sAPPβ, a product of the amyloidogenic cleavage pathway of amyloid precursor protein, fails to exhibit a proliferative effect in vitro and in vivo, in equimolar concentrations to sAPPα. These observations suggest that adulthood is an appropriate time window for an intervention that upregulates neurogenesis, such as enhancement of sAPPα levels, for the prevention of declining brain plasticity and cognitive function.

Keywords: Adulthood; Aging; Alzheimer's disease; Amyloid precursor protein; Cognition; Learning and memory; Neurogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / pathology*
  • Aging / physiology*
  • Amyloid beta-Protein Precursor / administration & dosage
  • Amyloid beta-Protein Precursor / pharmacology*
  • Amyloid beta-Protein Precursor / physiology
  • Animals
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Cerebral Ventricles / cytology
  • Cerebral Ventricles / pathology
  • Cognition Disorders / etiology
  • Cognition Disorders / pathology
  • Cognition Disorders / prevention & control
  • Dentate Gyrus / cytology
  • Dentate Gyrus / pathology
  • Injections, Intraventricular
  • Mice
  • Mice, Inbred C57BL
  • Neurogenesis / drug effects*
  • Neurogenesis / physiology
  • Neuronal Plasticity
  • Neurons / cytology*
  • Neurons / pathology
  • Recombinant Proteins
  • Solubility
  • Stem Cells / cytology*
  • Stem Cells / pathology


  • Amyloid beta-Protein Precursor
  • Recombinant Proteins