Progressive impairments in executive function in the APP/PS1 model of Alzheimer's disease as measured by translatable touchscreen testing

Amy Shepherd, Jeremiah K K.H. Lim, Vicky H H.Y. Wong, Ariel M M. Zeleznikow-Johnston, Leonid Churilov, Christine T T.O. Nguyen, Bang V V. Bui, Anthony J J. Hannan, Emma L L. Burrows

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

Executive function deficits in Alzheimer's disease (AD) occur early in disease progression and may be predictive of cognitive decline. However, no preclinical studies have identified deficits in rewarded executive function in the commonly used APPSwe/PS1∆E9 (APP/PS1) mouse model. To address this, we assessed 12-26 month old APP/PS1 mice on rewarded reversal and/or extinction tasks. 16-month-old, but not 13- or 26-month-old, APP/PS1 mice showed an attenuated rate of extinction. Reversal deficits were seen in 22-month-old, but not 13-month-old APP/PS1 animals. We then confirmed that impairments in reversal were unrelated to previously reported visual impairments in both AD mouse models and humans. Age, but not genotype, had a significant effect on markers of retinal health, indicating the deficits seen in APP/PS1 mice were directly related to cognition. This is the first characterisation of rewarded executive function in APP/PS1 mice, and has great potential to facilitate translation from preclinical models to the clinic.

Original languageEnglish
Pages (from-to)58-71
Number of pages14
JournalNeurobiology of Aging
Volume108
DOIs
Publication statusPublished - Dec 2021

Keywords

  • APP/PS1
  • Executive function
  • Extinction
  • Mice
  • Rodent
  • Touchscreen
  • Visual discrimination

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