Transgenic mice (Tg₂₅₇₆) overexpress amyloid precursor protein (APP) and develop plaques; hallmarks of Alzheimer's Disease (AD). Consequently, this mouse is considered a model of AD as deficits in Morris water maze learning are claimed to correlate with amyloid burden (Hsiao, 1996). However, we are unable to demonstrate any cognitive changes in these mice that relate to increased amyloid deposition. Amyloid deposits in these mice are observed by 10 months of age in several brain regions including olfactory bulbs. Presumed neurotoxic effects of amyloid could therefore interfere with the ability to discriminate odors. We exposed Tg₂₅₇₆ mice to an Y-maze odor discrimination task, presumably allowing us to describe a functional relevance of amyloid deposition in these mice. Three strains of mice, BL6/SJL, Tg+, and Tg-, and three age groups within the strains, young (9 mo), middle (11-12 mo) and aged (14-15 mo) were used. The animals were food-deprived such that 80% of initial body weight was maintained. Each animal was assigned a positive reinforcement (S+) odor (almond, lemon, peppermint) which when discriminated would result in a food reward. Animals were introduced into the Y-maze 6x for scent training prior to the discrimination session. Valence numbers were assigned to order of Y-maze arm entry for data analysis. There were no statistically significant main effects or interactive effects of strain and age suggesting these mice are not cognitively impaired.

References

1. Hsiao, K.; Chapman, P.; Nilsen, S.; Eckman, C.; Harigaya, Y.; Younkin, S.; Yang, F.; Cole, G. (1996). Correlative memory deficits, A ß elevation, and amyloid plaques in transgenic mice. Science, 274, 99-102.

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