Lifespan of male and female APP/PS1 and APPNL-F/NL-F mouse models of Alzheimer's disease

J Alzheimers Dis. 2025 May;105(1):56-61. doi: 10.1177/13872877251325878. Epub 2025 Mar 26.

Abstract

Alzheimer's disease (AD) disproportionately affects women, yet most preclinical research studies are male-centric. We performed lifespan analyses of male and female AD mouse models (APP/PS1 and APPNL-F/NL-F) and their shared genetic background control (C57BL/6). Survival curves support significant sex differences between genotypes. Minimal longevity revealed increased age in male APP/PS1, and decreased age in male APPNL-F/NL-F mice. Maximal longevity revealed an increased average age in males. Furthermore, median lifespan differed between sex and genotype. This study supports dimorphic survival in two mouse models of AD, emphasizing the need to examine mechanisms and treatments in both sexes.

Keywords: Alzheimer's disease; Kaplan-Meier estimate; amyloid-β; survival curve.

MeSH terms

  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / mortality
  • Amyloid beta-Protein Precursor* / genetics
  • Animals
  • Disease Models, Animal
  • Female
  • Humans
  • Longevity* / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Presenilin-1* / genetics
  • Sex Characteristics*

Substances

  • Amyloid beta-Protein Precursor
  • Presenilin-1