Spatial learning deficits in amyloid precursor protein 770 transgenic mice

Objective To determine whether learning deficits could be seen in transgenic mice expressi ng human amyloid precursor protein 770 (APP770).Methods Female heterozygous transgenic and nontransgenic mice aged 3, 6 and 9 months at the start of testing were used, with eight mice in each age group.All mice wer e subjected to various behavioral tasks including the Y-maze task and the Morri s water maze.After behavioral testing, the mice were sacrificed, and their bra in tissues were used for measuring the choline acetyltransferase (ChAT) activity . Results Nine-month-old transgenic mice exhibited spatial learning deficits in the Morr is water maze and in spontaneous alternation in the Y-maze, compared with those o f the age-matched non-transgenic mice.The behavioral changes accompanied a red uction of ChAT activity in the cortical and hippocampal regions of transgenic mi ce.On the other hand, these behavioral deficits were not observed in transgeni c mice either at 3 or at 6 months of age, in which ChAT activity remained unchan ged. Conclusions The present results show that the learning impairment observed in 9-month-old APP770 transgenic mice are accompanied by a decrease in cortical and hippo campal ChAT activities.This suggests that cholinergic deficits may be involved in the learning impairment observed in these APP770 mice.This model wi ll be a useful tool in advancing our understanding of the relationship between t he cholinergic system and the cognitive deficits observed in Alzheimer’s disease (AD).