Assessment of Visual Sustained Attention and Visual Spatial Integration in the APP/PS1, 5xFAD, and 3xTG Transgenic mouse models of Alzheimer's disease

In the course of Alzheimer’s Disease (AD) pathology, there is a progressive worsening of cognitive symptoms. One of the important steps in AD research has been to identify early behavioural symptoms that can be used as markers of further cognitive decline. Previous research with humans has shown that attentional deficits may emerge early in the disease course, prior to memory impairments. It has also been shown that deficits in visual spatial learning are also an early marker of further cognitive decline. While these behaviours have been characterized in humans, there has been very little research looking at attention and visual spatial learning in transgenic mouse models of AD. The goal of these experiments was to systematically characterize attention and visual spatial learning in three of the most used transgenic mouse models of AD. TO assess behaviour, we used newly developed touchscreen equipped operant chambers. We used the APP/PS1, 5xFAD, and 3xTG transgenic mouse models of AD in the current study. We also assessed sex differences by comparing male and female mice performance. To assess attention, we used the 5-choice serial reaction time task (5-CSRTT). Animals were run on the 5-CSRTT at 4, 7, and 10 months of age to look for behavioural changes related to neurological decline. Visual spatial learning was assessed with the paired associate learning (PAL) task at 4 months of age. It was found that 3xTG and 5xFAD transgenic mice show deficits in attention, with the 3xTG mice showing a very early phenotype at 4 months of age. The 3xTG and APP/PS1 male transgenic mice showed a significant impairment in visual spatial learning, while the 5xFAD show significant impairment in the retention of visual spatial memories. Overall, these three transgenic lines show significant differences between strains. This study demonstrates that the cognitive profiles of these transgenic lines are dramatically different, and that researchers should make important considerations when deciding on which strain to use for their research.