3xTgAD mice exhibit altered behavior and elevated Aβ after chronic mild social stress

Neurobiol Aging. 2012 Apr;33(4):830.e1-12. doi: 10.1016/j.neurobiolaging.2011.07.005. Epub 2011 Aug 19.


Chronic stress may be a risk factor for developing Alzheimer's disease (AD), but most studies of the effects of stress in models of AD utilize acute adverse stressors of questionable clinical relevance. The goal of this work was to determine how chronic psychosocial stress affects behavioral and pathological outcomes in an animal model of AD, and to elucidate underlying mechanisms. A triple-transgenic mouse model of AD (3xTgAD mice) and nontransgenic control mice were used to test for an affect of chronic mild social stress on blood glucose, plasma glucocorticoids, plasma insulin, anxiety, and hippocampal amyloid β-particle (Aβ), phosphorylated tau (ptau), and brain-derived neurotrophic factor (BDNF) levels. Despite the fact that both control and 3xTgAD mice experienced rises in corticosterone during episodes of mild social stress, at the end of the 6-week stress period 3xTgAD mice displayed increased anxiety, elevated levels of Aβ oligomers and intraneuronal Aβ, and decreased brain-derived neurotrophic factor levels, whereas control mice did not. Findings suggest 3xTgAD mice are more vulnerable than control mice to chronic psychosocial stress, and that such chronic stress exacerbates Aβ accumulation and impairs neurotrophic signaling.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Alzheimer Disease / blood
  • Alzheimer Disease / complications*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / genetics
  • Analysis of Variance
  • Animals
  • Anxiety / etiology*
  • Behavior, Animal / physiology*
  • Blood Glucose / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism
  • Disease Models, Animal
  • Fasting
  • Glucocorticoids / blood
  • Hippocampus / pathology
  • Humans
  • Insulin / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation / genetics
  • Presenilin-1 / genetics
  • Social Behavior*
  • Stress, Psychological / physiopathology*
  • Time Factors
  • tau Proteins / genetics
  • tau Proteins / metabolism


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Blood Glucose
  • Brain-Derived Neurotrophic Factor
  • Glucocorticoids
  • Insulin
  • PSEN1 protein, human
  • Presenilin-1
  • tau Proteins