Impaired spatial learning in the APPSwe + PSEN1ΔE9 bigenic mouse model of Alzheimer’s disease

Top Cited Papers
Open Access
Publisher Website
Google Scholar
Abstract
Mice co‐expressing the Swedish amyloid precursor protein mutation (APPSwe) and exon 9 deletion (ΔE9) 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 APPSwe + PSEN1ΔE9 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 APPSwe + PSEN1ΔE9 mice were unimpaired on tests of memory that did not involve learning the rules governing spatial associations.