Cognitive and physical activity differently modulate disease progression in the amyloid precursor protein (APP)-23 model of Alzheimer's disease

Biol Psychiatry. 2006 Dec 15;60(12):1314-23. doi: 10.1016/j.biopsych.2006.04.004. Epub 2006 Jun 27.


Background: In aging mice, activity maintains hippocampal plasticity and adult hippocampal neurogenesis at a level corresponding to a younger age. Here we studied whether physical exercise and environmental enrichment would also affect brain plasticity in a mouse model of Alzheimer's disease (AD).

Methods: Amyloid precursor protein (APP)-23 mice were housed under standard or enriched conditions or in cages equipped with a running wheel. We assessed beta-amyloid plaque load, adult hippocampal neurogenesis, spatial learning, and mRNA levels of trophic factors in the brain.

Results: Despite stable beta-amyloid plaque load, enriched-living mice showed improved water maze performance, an up-regulation of hippocampal neurotrophin (NT-3) and brain-derived neurotrophic factor (BDNF) and increased hippocampal neurogenesis. In contrast, despite increased bodily fitness, wheel-running APP23 mice showed no change in spatial learning and no change in adult hippocampal neurogenesis but a down-regulation of hippocampal and cortical growth factors.

Conclusions: We conclude that structural and molecular prerequisites for activity-dependent plasticity are preserved in mutant mice with an AD-like pathology. Our study might help explain benefits of activity for the aging brain but also demonstrates differences between physical and more cognitive activity. It also suggests a possible cellular correlate for the dissociation between structural and functional pathology often found in AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / chemically induced
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / psychology*
  • Amyloid beta-Protein Precursor / toxicity*
  • Animals
  • Brain / pathology
  • Brain-Derived Neurotrophic Factor / biosynthesis
  • Brain-Derived Neurotrophic Factor / genetics
  • Cell Count
  • Cerebral Cortex / metabolism
  • Cognition / physiology*
  • Disease Progression
  • Environment
  • Female
  • Fibroblast Growth Factor 2 / biosynthesis
  • Hippocampus / metabolism
  • Insulin-Like Growth Factor I / biosynthesis
  • Maze Learning / physiology
  • Mice
  • Mice, Transgenic
  • Motor Activity / physiology*
  • Nerve Growth Factor / biosynthesis
  • Nerve Growth Factor / genetics
  • Neurotrophin 3 / biosynthesis
  • Neurotrophin 3 / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / genetics


  • Amyloid beta-Protein Precursor
  • Brain-Derived Neurotrophic Factor
  • Neurotrophin 3
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Insulin-Like Growth Factor I
  • Nerve Growth Factor