Longitudinal assessment of cognitive function in the APPswe/PS1dE9 mouse model of Alzheimer's-related beta-amyloidosis

Neurobiol Aging. 2023 Aug:128:85-99. doi: 10.1016/j.neurobiolaging.2023.03.010. Epub 2023 Apr 2.

Abstract

Preclinical models of Alzheimer's disease (AD)-related cognitive decline can be useful for developing therapeutics. The current study longitudinally assessed short-term memory, using a delayed matching-to-position (DMTP) task, and attention, using a 3-choice serial reaction time (3CSRT) task, from approximately 18 weeks of age through death or 72 weeks of age in APPswe/PS1dE9 mice, a widely used mouse model of AD-related amyloidosis. Both transgenic (Tg) and non-Tg mice exhibited improvements in DMTP accuracy over time. Breaks in testing reduced DMTP accuracy but accuracy values quickly recovered in both Tg and non-Tg mice. Both Tg and non-Tg mice exhibited high accuracy in the 3CSRT task with breaks in testing briefly reducing accuracy values equivalently in the 2 genotypes. The current results raise the possibility that deficits in Tg APPswe/PS1dE9 mice involve impairments in learning rather than declines in established performances. A better understanding of the factors that determine whether deficits develop will be useful for designing evaluations of potential pharmacotherapeutics and may reveal interventions for clinical application.

Keywords: APPswe/PS1dE9 mice; Alzheimer’s disease; Attention; Delayed matching-to-position; Memory; Serial reaction time.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alzheimer Disease* / psychology
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Protein Precursor / genetics
  • Amyloidosis*
  • Animals
  • Cognition
  • Disease Models, Animal
  • Mice
  • Mice, Transgenic
  • Presenilin-1 / genetics

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Presenilin-1