Impairments in neurogenesis are not tightly linked to depressive behavior in a transgenic mouse model of Alzheimer's disease

PLoS One. 2013 Nov 14;8(11):e79651. doi: 10.1371/journal.pone.0079651. eCollection 2013.


Alzheimer's disease (AD), the most common cause of dementia, is also associated with depression. Although the precise mechanisms that lead to depression in AD are unknown, the impairments in adult hippocampal neurogenesis observed in AD may play a role. Adult-born neurons play a critical role in regulating both cognition and mood, and reduced hippocampal neurogenesis is associated with depression in other neurological disorders. To assess the relationship between Alzheimer's disease, neurogenesis, and depression, we studied human amyloid precursor protein (hAPP) transgenic mice, a well-characterized model of AD. We report that reductions in hippocampal neurogenesis are evident early in disease progression in hAPP mice, but a mild depressive phenotype manifests only in later stages of disease. We found that hAPP mice exhibited a reduction in BrdU-positive cells in the subgranular zone of the dentate gyrus in the hippocampus, as well as a reduction in doublecortin-expressing cells, relative to nontransgenic controls at 5-7 months of age. These alterations in neurogenesis appeared to worsen with age, as the magnitude of reduction in doublecortin-expressing cells was greater in hAPP mice at 13-15 months of age. Only 13-15 month old hAPP mice exhibited depressive behavior in the tail suspension test. However, mice at both age groups exhibited deficits in spatial memory, which was observed in the Morris water maze test for hippocampus-dependent memory. These findings indicate that neurogenesis impairments are accompanied by cognitive deficits, but are not tightly linked to depressive behavior in hAPP mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / psychology*
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Behavior, Animal
  • Depression*
  • Disease Models, Animal
  • Female
  • Genotype
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Male
  • Memory
  • Mice
  • Mice, Transgenic
  • Neurogenesis*
  • Phenotype


  • Amyloid beta-Protein Precursor

Grant support

The Chin lab is grateful for support from the Alzheimer's Association grant NIRG-11-205769 ( and the Margaret Q. Landenberger Research Foundation (no public URL), from whom funds were used to partially support lab staff and animal maintenance during the course of this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.