Behavioral and neurobiological markers of Alzheimer's disease in Ts65Dn mice: Effects of estrogen

Christopher L. Hunter, Heather A. Bimonte-Nelson, Mathew Nelson, Christopher B. Eckman, Ann Charlotte Granholm

Research output: Contribution to journalArticlepeer-review

68 Scopus citations


Individuals with Down's syndrome (DS) develop neuropathological features similar to Alzheimer's disease (AD) early in life, including dementia, accumulation of β-amyloid, and irregular phosphorylation of tau proteins. Ts65Dn mice, an animal model of DS, provide a unique method to investigate the mechanisms related to AD-like symptoms in DS and possible therapeutic interventions. Ts65Dn mice undergo a decline in cholinergic phenotype and cognitive deterioration beginning at 6-8 months of age. In middle-aged female Ts65Dn mice, estrogen supplementation alleviated these cholinergic and cognitive impairments. The current study investigated AD-like markers and the effects of estrogen in male Ts65Dn mice. Estrogen treatment prior to behavioral testing did not improve cognitive deficits in 6-month-old male Ts65Dn mice, but decreased total and phosphorylated (pS199) tau in the entorhinal cortex compared to normosomic animals. Hippocampal β-amyloid(1-42) levels were increased in Ts65Dn animals, regardless of estrogen treatment. These findings further support Ts65Dn mice as a model for specific AD-like symptoms, and demonstrate that estrogen treatment of this type does not improve the cognitive ability of male Ts65Dn mice.

Original languageEnglish (US)
Pages (from-to)873-884
Number of pages12
JournalNeurobiology of Aging
Issue number7
StatePublished - Aug 2004
Externally publishedYes


  • Alzheimer's disease
  • Down's syndrome
  • Estradiol
  • Tau
  • Tau (pS199)
  • Working memory load
  • β-Amyloid

ASJC Scopus subject areas

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


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