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

Genes Brain Behav. 2007 Feb;6(1):54-65. 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

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


  • Amyloid beta-Protein Precursor
  • Presenilin-1