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

Sarah M. Rothman, Nathan Herdener, Simonetta Camandola, Sarah J. Texel, Mohamed R. Mughal, Wei Na Cong, Bronwen Martin, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


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.

Original languageEnglish (US)
JournalNeurobiology of Aging
Issue number4
StatePublished - Apr 2012
Externally publishedYes


  • Alzheimer's disease
  • Amyloid oligomers
  • BDNF
  • Corticosterone
  • Hippocampus
  • Psychosocial stress

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology


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