Austin Health

Title
Progressive impairments in executive function in the APP/PS1 model of Alzheimer's disease as measured by translatable touchscreen testing.
Publication Date
2021-12
Author(s)
Shepherd, Amy
Lim, Jeremiah K H
Wong, Vicky H Y
Zeleznikow-Johnston, Ariel M
Churilov, Leonid
Nguyen, Christine T O
Bui, Bang V
Hannan, Anthony J
Burrows, Emma L
Subject
APP/PS1
Executive function
Extinction
Mice
Rodent
Touchscreen
Visual discrimination
Type of document
Journal Article
OrcId
0000-0002-8929-5735
0000-0002-9807-6606
0000-0001-7532-8922
0000-0002-6675-4679
0000-0002-7497-8242
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.
Link
Citation
Neurobiology of aging 2021; 108: 58-71
Jornal Title
Neurobiology of aging

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