Transgenic mice expressing mutant human amyloid precursor protein (APPswe) and presenilin-1 (PS1ΔE9) develop amyloid deposits as early as 4 months of age. We have shown previously that this is associated with a progressive loss of serotonin and norepinephrine neurotransmitter levels in the hippocampus later in life. Furthermore, hippocampal BDNF
protein levels are increased in APP/PS1 mice, possibly as a response to neurodegeneration in a brain region important for learning and memory. In the current pilot study, we evaluated the effects of amyloid deposition on anxiety-like behavior, exploratory activity and route learning in a relatively small group (N=27) of 17-month-old wildtype, APP, PS1 and APP/PS1 mice. All testing was conducted during the dark phase in food and water satiated mice. In the elevated plus maze, modestly significant main effects of time in the closed arms, closed arm entries and total arm entries were observed, however, no significant individual genotype comparisons were evident. In the open field, there were no significant differences in total distance traveled. We also evaluated behavior in the Lashley III maze, a low stress learning and memory test. This is a route-learning task that does not rely on aversive stimuli or visual cues. There was a significant main effect of genotype in start latency into the maze, which was manifest as increased start latency in APP and APP/PS1 genotypes on the first day of maze learning. There were no significant differences in days to criterion (number of days to traverse the maze with zero or one error for two consecutive nights) and all genotypes of mice took 5-6 nights on average to learn the maze. Interestingly, there was a trend toward an increase in learning index (number of correct path segments as a ratio of total path segments) [F(3,23)=2.66; p=0.072] with all transgenic groups (APP only, PS1 only and APP/PS1 double transgenic) making more correct path choices. We are currently assessing serotonergic innervation and neurogenesis by immunocytochemistry in the brains from these mice. Further testing with larger sample sizes and across different ages will be necessary to better interpret the behavioral results, however, the current results suggest that there are no changes in anxiety-related behavior or overall activity in mice overexpressing mutant human amyloid precursor protein and presenilin-1.