Comprehensive touchscreen characterisation of the APP/PS1 mouse model of Alzheimer’s disease
AuthorShepherd, Amy Louise
AffiliationFlorey Department of Neuroscience and Mental Health
Document TypePhD thesis
Access StatusThis item is embargoed and will be available on 2021-08-14. This item is currently available to University of Melbourne staff and students only, login required.
Alzheimer’s disease is the most common form of dementia, and represents one of the biggest health challenges of our time. As such, it has been the subject of intense research for the past 20 years, but, as of yet, no effective disease-modifying treatments have passed clinical trials. The use of AD mouse models to identify potential treatments is a predominant method used by the field, but cognition is not assessed in these models in a comparable way to the clinic. This body of work was interested in using rodent touchscreen technology to comprehensively characterise clinically relevant cognitive domains in the APP/PS1 mouse model of AD. Four cohorts of APP/PS1 mice (and wild-type littermate controls) from 8-26 months of age underwent touchscreen tasks assessing attention, impulsive and compulsive behaviours and executive function, as well as hippocampal-dependent associative learning, pattern separation and working memory. Additionally, a touchscreen-exposed and naïve cohort of 12-month-old animals underwent 2 traditional behavioural tasks that are well characterised in the literature, the Morris water maze and forced alternation. APP/PS1 mice showed slightly increased impulsive and compulsive behaviour at 11 months of age, as well as a subtle executive function deficit at 16 months of age that became increasingly severe to 26 months of age. At 12 months of age, APP/PS1 mice showed no changes on touchscreen-assessed associative learning or attention, nor in Morris water maze or forced alternation. Furthermore, APP/PS1 mice showed no changes in basic learning or vision function up to 26 months of age, nor in working memory or pattern separation up to 16 months of age. Cell proliferation in the hippocampus was affected by age but not genotype at 12 and 21 months of age. As one would expect hippocampal-dependent deficits to occur prior to executive dysfunction, we became interested in how environmental factors may change disease progression in AD mouse models. We completed a systematic review on the effects of exercise and environmental enrichment (EE) on AD mouse models, and found that both EE and exercise consistently improved cognition and increased neurogenesis and synaptic plasticity markers, while the effects on amyloid were inconsistent. Thus, we hypothesized that the touchscreen testing paradigm may have improved hippocampal function and thus delayed onset of symptoms in the APP/PS1 mice. This body of work provides the first full characterization of any AD mouse model across various ages, and the battery developed can be used for future studies.
KeywordsAlzheimer's disease; APP/PS1 mouse; preclinical animal model; touchscreen
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