Impaired spatial learning in the APPSwe + PSEN1DeltaE9 bigenic mouse model of Alzheimer's disease.

Reiserer RS, Harrison FE, Syverud DC, McDonald MP
Genes Brain Behav. 2007 6 (1): 54-65

PMID: 17233641 · DOI:10.1111/j.1601-183X.2006.00221.x

Mice co-expressing the Swedish amyloid precursor protein mutation (APP(Swe)) and exon 9 deletion (DeltaE9) of the PSEN1 gene begin to develop amyloid plaques at 6-7 months of age. We demonstrate here a spatial learning deficit in 7-month-old APP(Swe) + PSEN1DeltaE9 bigenic mice using an adaptation of the Barnes maze. Mice were first trained on a cued target followed by a hidden-target condition. Although bigenic mice quickly learned the cued-target version of the task, they were significantly impaired when switched to the hidden-target version. In contrast, a separate group of double-transgenic mice trained first on the spatial hidden-target version of the task were unimpaired relative to wild-type controls. We propose that processes such as general rule learning, context learning and exploratory habituation exert a greater influence when the testing environment is novel and overshadow the spatial memory deficit in naive bigenic mice. However, when cued-target training is conducted first, these processes habituate and the spatial learning deficit is unmasked. Seven-month-old APP(Swe) + PSEN1DeltaE9 mice were unimpaired on tests of memory that did not involve learning the rules governing spatial associations.

MeSH Terms (17)

Alzheimer Disease Amyloid beta-Protein Precursor Animals Anxiety Brain Disease Models, Animal Exploratory Behavior Female Gene Deletion Male Maze Learning Mice Mice, Neurologic Mutants Mice, Transgenic Presenilin-1 Space Perception Spatial Behavior

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