Locomotor activity, emotionality, sensori-motor gating, learning and memory in the APPswe/PS1dE9 mouse model of Alzheimer's disease

The APPswe/PS1dE9 mouse (line 85) is a double transgenic model of Alzheimer's disease (AD) with familial amyloid precursor protein and presenilin-1 mutations. These mice develop age-related behavioral changes reflective of the neuropsychiatric symptoms (altered anxiety-like behaviour, hyperactivity) and cognitive dysfunction (impaired learning and memory) observed in AD. The APPswe/PS1dE9 mouse has been used to examine the efficacy of therapeutic interventions on behaviour, despite previous difficulties in replicating behavioural phenotypes. Therefore, the purpose of this study was to establish the reliability of these phenotypes by further characterizing the behaviour of male APPswe/PS1dE9 and wild-type mice between 7 and 14 months of age. Mice were tested on the open-field over 5-days to examine emotionality, locomotor activity and inter-session habituation. Mice were also tested on the repeated-reversal water maze task and spontaneous alternation on the Y-maze to assess working memory. Sensori-motor gating was examined with acoustic startle and pre-pulse inhibition. Lastly contextual and cued (trace) memory was assessed with fear conditioning. The results show that among non-cognitive behaviours, APPswe/PS1dE9 mice have normal locomotor activity, anxiety-like behavior, habituation and sensori-motor gating. However, APPswe/PS1dE9 mice show impaired working memory on the repeated-reversal water-maze and impaired memory in contextual but not trace-cued fear conditioning. These results indicate that the APPswe/PS1dE9 (line 85) mice have deficits in some types of hippocampal-dependent learning and memory and, at the ages tested, APPswe/PS1dE9 mice model cognitive dysfunction but not neuropsychiatric symptoms.