Cognitive decline in Tg2576 mice shows sex-specific differences and correlates with cerebral amyloid-beta

Behav Brain Res. 2019 Feb 1:359:408-417. doi: 10.1016/j.bbr.2018.11.022. Epub 2018 Nov 17.

Abstract

Patients suffering from Alzheimer's disease show a sex-dependent decline of cognitive function. The aim of this investigation was to show these differences in an animal model for Alzheimer's disease and to determine whether this effect is correlated to amyloid-beta-induced pathophysiological changes. Therefore, we assessed cognitive performance with the modified hole-board test in female and male Tg2576 and wild type mice at the age of 6, 8, 10, 12, 14, and 16 months and correlated these findings to the total amount of soluble amyloid-beta and insoluble amyloid deposits in the brain. Tg2576 mice perform worse than wild types. Female Tg2576 mice develop an accentuated cognitive impairment (wrong choice total) beginning at the age of 12 months compared to their male littermates. Alterations in the mice's behaviour do not show interference with these deficits. Cognitive impairment is correlated to the amount of soluble amyloid-beta and insoluble amyloid deposits in the brain in a sex-dependent manner.

Keywords: Alzheimer’s disease; Amyloid-beta; Cognitive impairment; Modified hole-board test; Sex differences; Tg2576.

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Cerebral Cortex / metabolism*
  • Cerebral Cortex / pathology
  • Cognitive Dysfunction / metabolism*
  • Cognitive Dysfunction / pathology
  • Disease Models, Animal
  • Female
  • Male
  • Memory / physiology
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Sex Characteristics*

Substances

  • Amyloid beta-Peptides