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T. HANANIA, D. HAVAS, I. MORGANSTERN, E. SABATH, P. KABITZKE, M. MAZZELLA, K. COX, J. BERGER, M. WINDISCH, D. BRUNNER, V. ALEXANDROV

Background:
Tg 2576 mice are one of the standard models for AD research. The APP/PS1 mice are produced by cross, breeding of this model with PS1 tg mice. PS1 mutatn changes the processing of APP, increasing the proportion of pro-aggregatory ABeta42, accelerating formation of plaque pathology and functional deficits. It is the first time that both models were compared using proprietary, very sensitive behavioral tests that may have the capability to increase even predictive drug testing in animals models of AD. It was of interest to explore to what extent differences in behavioral performance between both mouse lines is reflected by differences in AD-like brain pathology. This can be important also for interpretation of results from treatment trials.

Methods:
Female 13 and 52 weeks old tg2576 and APP/PS1 mice were investigated using SmartCube™ (spontaneous behavior), NeuroCube™ (Measurement of gait and motor function) and the PhenoCube™ (social interaction, day/ night activity and cognition) Systems. At the end of the experiments mice brains were investigated for differences in plaque pathology, astro-glioses and micro-glia activation using quantitative immunohistochemistry.

Results:
In all behavioral examinations there was a clear difference to age matched wt-controls which increased with age. The differences between the two tg-mouse lines are smaller than the distinction from the controls. In general APP/PS1 mice perform worse than the tg 2576 mice, except in the investigation of social interaction, where tg 2576 mice progress with increased interaction, but the phenotype of the APPPS1 mice is closer to normal situation with increasing age. Detailed immune-histochemical examination is trying to connect this to differences in brain pathology.

Conclusions:
The data show that also in this new, very detailed behavioral tests there is a clear distinction between the two genotypes, which may relate mainly to differences in APP processing due to the PS1 mutation. The relationship between behavior and findings in brain IHC suggest also the importance of choosing the right animal model for efficacy testing