Impaired spatial learning in the APPSwe + PSEN1ΔE9 bigenic mouse model of Alzheimer’s disease
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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The Barnes maze protocol used allowed detection of spatial learning deficits in PS1-APP mice trained first with the cued version followed by the non-cued version.
“We used a protocol that allowed detection of spatial learning deficits in PS1-APP mice that had been trained first with the cued version followed by the non-cued version (23).”
From Heterozygous CX3CR1 Deficiency in Microglia Restores Neuronal β-Amyloid Clearance Pathways and Slows Progression of Alzheimer's Like-Disease in PS1-APP Mice (2019) · cites this paper as [23]
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- Authors
- Reiserer, R. S., Harrison, F. E., Syverud, D. C., & McDonald, M. P.
- Affiliations
- Vanderbilt University (US)
- Corresponding author
- McDonald, M. P.
- Venue
- Genes, Brain and Behavior
- Publisher
- Wiley
- Published
- 2006-04-13
- Volume
- 6
- Issue
- 1
- Pages
- 54-65
- ISSN
- 1601-183X (ISSN-L)
- 1601-1848
- OpenAlex
- W2055883416
- Cited by
- 324
- References
- 4
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 18 · 2023: 21 · 2022: 10 · 2021: 23 · 2020: 15 · 2019: 18 · 2018: 30 · 2017: 26 · 2016: 20 · 2015: 17 · 2014: 19 · 2013: 21 · 2012: 16
- FWCI
- 6.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Genes Brain & Behavior (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG022439, AG-022439)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD015052, HD015052)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Keywords
- Alzheimer's disease, APPswe, spatial learning, spatial memory, amyloid plaques, Barnes maze, rule induction, contextual learning, transgenic mouse model
- MeSH terms
- Alzheimer Disease, Animals, Anxiety, Brain, Disease Models, Animal, Exploratory Behavior, Female, Male, Mice, Neurologic Mutants, Mice, Transgenic, Space Perception, Spatial Behavior, Amyloid beta-Protein Precursor, Gene Deletion, Maze Learning, Mice, Presenilin-1
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