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

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

doi:10.1016/j.neurobiolaging.2021.08.004

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

Neurobiol Aging. 2021 Dec:108:58-71. doi: 10.1016/j.neurobiolaging.2021.08.004. Epub 2021 Aug 12.

Authors

Amy Shepherd¹, Jeremiah K H Lim², Vicky H Y Wong², Ariel M Zeleznikow-Johnston³, Leonid Churilov⁴, Christine T O Nguyen², Bang V Bui², Anthony J Hannan⁵, Emma L Burrows⁶

Affiliations

¹ Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Victoria, Australia.
² Department of Optometry and Vision Sciences, University of Melbourne, Victoria, Australia.
³ Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Victoria, Australia; Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Victoria, Australia.
⁴ Department of Medicine (Austin Health) and Melbourne Brain Centre at Royal Melbourne Hospital, Melbourne Medical School, Parkville, Australia.
⁵ Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Victoria, Australia; Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia.
⁶ Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Victoria, Australia. Electronic address: emma.burrows@florey.edu.au.

PMID: 34509856
DOI: 10.1016/j.neurobiolaging.2021.08.004

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.

Keywords: APP/PS1; Executive function; Extinction; Mice; Rodent; Touchscreen; Visual discrimination.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging / physiology
Aging / psychology
Alzheimer Disease / physiopathology*
Alzheimer Disease / psychology*
Amyloid beta-Protein Precursor / genetics
Animals
Disease Models, Animal
Disease Progression
Executive Function*
Mice, Transgenic
Neuropsychological Tests*
Presenilin-1 / genetics
Reward
Touch / physiology*
Visual Perception / physiology

Substances

Amyloid beta-Protein Precursor
Presenilin-1