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

Abstract

Mice co-expressing the Swedish amyloid precursor protein mutation (APP Swe ) and exon 9 deletion (DE9) 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 + PSEN1DE9 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 + PSEN1DE9 mice were unimpaired on tests of memory that did not involve learning the rules governing spatial associations.

Characterization of AD-like phenotype in aged APPSwe/PS1dE9 mice

“…Previous studies report that APP/PS1 mice show reference memory impairments by 3 months of age and persist throughout life (Reiserer et al 2007;Bernardo et al 2009;O'Leary and Brown 2009). By comparing these results with our previous Y-maze test for behavioral analysis of 11-12-month-old APP/PS1 mice , we found that 24-month-old APP/PS1 cohorts show more severe working and reference memory impairment.…”

Intranasal insulin alleviates cognitive deficits and amyloid pathology in young adult APP swe/ PS 1dE9 mice

“…These observations are consistent with a previous study showing obvious thigmotactic behavior in 7‐month‐old APP/PS1 mice of the same strain (Ferguson et al ., 2013). However, the anxiety levels of these transgenic mice are inconsistent among different studies, and it seems that anxiety‐related behaviors are task‐specific (Lalonde et al ., 2004; Reiserer et al ., 2007). Other anxiety‐related tests such as light–dark test and elevated plus maze are needed to validate the anxiety level of these mice and the anxiolytic effect of intranasal insulin in these mice.…”

A GPCR/secretase complex regulates β- and γ-secretase specificity for Aβ production and contributes to AD pathogenesis

“…APP/ PS double-transgenic mice coexpress a chimeric mouse/ human APP Swedish mutant (APPswe) and a mutant human PS1 (PS1ΔE9) [52]. These transgenic mice display an aggressive onset of age-dependent neuritic Aβ deposition in the cortex and hippocampus, and begin to show memory deficits at the age of 6 months [53,54]. Drug administration began prophylactically at 4 months of age (that is, about 2 months before the onset of phenotype).…”