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

Full Abstract

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.

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Author information

Author/s: Reiserer, R S (RS); Harrison, F E (FE); Syverud, D C (DC); McDonald, M P (MP);

Affiliation: Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37232-0325, USA.

Grants: AG022439 (Agency:NIA NIH HHS) ; HD015052 (Agency:NICHD NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Genes, brain, and behavior (Genes Brain Behav), published in England. (Language: eng)

Reference: 2007-Feb; vol 6 (issue 1) : pp 54-65

Dates: Created 2007/01/19; Completed 2007/03/20; Revised 2007/12/03;

PMID: 17233641, status: MEDLINE (last retrieval date: 12/26/2008)

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Alzheimer Disease - genetics; metabolism
Amyloid beta-Protein Precursor - genetics; metabolism
Animals
Anxiety - genetics; metabolism
Brain - metabolism
Disease Models, Animal
Exploratory Behavior - physiology
Female
Gene Deletion

Gene Deletion
Male
Maze Learning - physiology
Mice
Mice, Neurologic Mutants
Mice, Transgenic
Presenilin-1 - genetics; metabolism
Space Perception - physiology
Spatial Behavior - physiology

Associated Chemicals: Amyloid beta-Protein Precursor (0) ; Presenilin-1 (0)

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