Sex differences between APPswePS1dE9 mice in A-beta accumulation and pancreatic islet function during the development of Alzheimer's disease

Lab Anim. 2016 Aug;50(4):275-85. doi: 10.1177/0023677215615269. Epub 2015 Oct 30.

Abstract

The pathogenesis of Alzheimer's disease (AD), a type of neurodegenerative disease characterized by learning and memory impairment, is often associated with pathological features, such as amyloid-beta (Aβ) accumulation and insulin resistance. The transgenic mouse, APPswePS1dE9 (APP/PS1), is one of the most commonly used animal models in pathogenesis studies of AD. The purpose of this study is to investigate the sex differences between APP/PS1 mice in the pathogenesis of AD. The impairment of glucose and insulin tolerance was found to develop earlier in male APP/PS1 mice than in females. Plasma insulin levels were significantly decreased in male APP/PS1 mice, while total cholesterol levels in male APP/PS1 mice were higher than those in females. Triglyceride levels in male mice in both the wild-type (WT) and APP/PS1 groups were higher than in their female littermates. Soluble and insoluble Aβ levels in female APP/PS1 mouse brains were higher than those in males. And the learning and memorizing abilities of female APP/PS1 mice were poorer than those of males. Our results concluded that there were sex differences in Aβ formation, pancreatic islet function and insulin sensitivity between male and female APP/PS1 mice during the pathogenesis of AD.

Keywords: APPswePS1dE9 mouse; Alzheimer’s disease; sex difference.

MeSH terms

  • Alzheimer Disease / etiology
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Body Weight
  • Brain / metabolism
  • Disease Models, Animal
  • Female
  • Glucose Tolerance Test
  • Humans
  • Insulin / blood
  • Islets of Langerhans / physiopathology*
  • Lipids / blood
  • Male
  • Memory*
  • Mice
  • Mice, Transgenic
  • Sex Characteristics
  • Spatial Learning*

Substances

  • Amyloid beta-Peptides
  • Insulin
  • Lipids