Impaired spatial learning in the APPSwe + PSEN1DeltaE9 bigenic mouse model of Alzheimer's disease.
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.
Reiserer
R S
RS
Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232-0325, USA.
Harrison
F E
FE
Syverud
D C
DC
McDonald
M P
MP
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D017353:Gene Deletion; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism*; D013028:Space Perception / Q000502:physiology; D013037:Spatial Behavior / Q000502:physiology*
D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1