Amyloid β and impairment in multiple memory systems in older transgenic APP TgCRND8 mice
Abstract
The relationship between amyloid beta and cognitive dysfunction in mouse models of Alzheimer's disease has been evaluated predominantly with the spatial reference memory version of the water maze task. However, as Alzheimer's disease encompasses decline in multiple memory systems, it is important to also utilize non‐spatial tasks to fully characterize the role of amyloid on behaviour in animal models. We used the TgCRND8 mouse model of Alzheimer's disease to evaluate the effect of amyloid on spatial reference memory, as well as on the non‐spatial task of acquisition of conditioned taste aversion, and on the procedural task of swimming to a visible platform. We demonstrate that 8‐ to 12‐month‐old TgCRND8 mice are significantly impaired in all three tasks, and that the levels of soluble amyloid beta are significantly correlated with impairment in spatial reference memory, but not with impairment in conditioned taste aversion or swimming to a visible platform. Insoluble fractions of amyloid, which correspond closely to amyloid plaque burden in the brain, are not associated with any behavioural measure. Our study extends the characterization of the model to stages of advanced amyloid pathology and demonstrates that older TgCRND8 mice are impaired in multiple memory systems, including procedural tasks, which are spared at younger ages. The lack of association between amyloid plaques and memory decline supports clinical findings in Alzheimer's patients.
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The chosen experimental paradigms were successfully used in the lab to demonstrate impairment in APP CRND8 mice.
“The chosen experimental paradigms were successfully used in our lab to demonstrate impairment in APP CRND8 mice, and focused on spatial learning and reference memory evaluated in WM test [9,10,13] and conditioned taste aversion, a form of Pavlovian associative learning, [34], in addition to the context and tone conditioned fear memory paradigm [25]”
From Normal cognition in transgenic BRI2-Aβ mice (2013) · cites this paper as [10]
Interaction with testing environment or personnel cannot explain the discrepancy, since the cognitive tests in the present study were run by the same PI and assistant as previously published work on APP CRND8 mice.
“In addition, interaction with testing environment [38,39], or personnel cannot explain the discrepancy, since the cognitive tests in the present study were run by the same PI (CJ) and assistant (AH) as our previously published work on APP CRND8 mice [10,25,34].”
From Normal cognition in transgenic BRI2-Aβ mice (2013) · cites this paper as [10]
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1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
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“Our results confirm recently reported findings that soluble higher molecular weight fractions of Aβ are selectively implicated in the decline of spatial reference memory in another mouse model of AD (Cheng et al. 2007; Lesne et al. 2006, 2008).”
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“The extraction and quantitation of sodium dodecyl sulfate (SDS)soluble and formic acid (FA)-soluble Aβ fractions were performed as previously described (Kawarabayashi et al. 2001).”
BackgroundMethodThe Alzheimer's Aβ peptide induces neurodegeneration and apoptotic cell death in transgenic mice
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Webster, S. J., Bachstetter, A. D., Nelson, P. T., Schmitt, F. A., & Van Eldik, L. J. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00088 · Cited by 755 · see citing works
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Normal cognition in transgenic BRI2-Aβ mice
Kim, J., Chakrabarty, P., Hanna, A., March, A., Dickson, D. W., Borchelt, D. R., Golde, T., & Janus, C. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-15 · Cited by 83 · see citing works
Self-citationUltrasound delivery of a TrkA agonist confers neuroprotection to Alzheimer-associated pathologies
Xhima, K., Markham-Coultes, K., Hahn Kofoed, R., Saragovi, H. U., Hynynen, K., & Aubert, I. (2022) · Brain · doi:10.1093/brain/awab460 · Cited by 43 · see citing works
- Authors
- Hanna, A., Horne, P., Yager, D., Eckman, C., Eckman, E., & Janus, C.
- Affiliations
- Mayo Clinic (US)
- University of Toronto (CA)
- Corresponding author
- Janus, C.
- ORCID
- Venue
- Genes, Brain and Behavior
- Publisher
- Wiley
- Published
- 2009-10
- Volume
- 8
- Issue
- 7
- Pages
- 676-684
- ISSN
- 1601-183X (ISSN-L)
- 1601-1848
- OpenAlex
- W1996946390
- Cited by
- 20
- References
- 6
- Citations by year
- 2024: 1 · 2021: 2 · 2018: 1 · 2017: 1 · 2015: 2 · 2014: 3 · 2013: 4 · 2012: 2
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Genes Brain & Behavior (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS048554, R01NS048554)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- amyloid-beta, Alzheimer's disease, TgCRND8 mice, transgenic mouse model, spatial reference memory, conditioned taste aversion, procedural memory, amyloid plaques, cognitive impairment, memory systems
- MeSH terms
- Alzheimer Disease, Animals, Avoidance Learning, Brain, Disease Models, Animal, Female, Humans, Male, Memory Disorders, Mice, Inbred C57BL, Mice, Transgenic, Nerve Net, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Disease Progression, Genetic Predisposition to Disease, Mice, Plaque, Amyloid
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