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Cited by 38Alzheimer's disease research and treatmentsMemory and Neural MechanismsDementia and Cognitive Impairment Research

Age-related increase in amyloid plaque burden is associated with impairment in conditioned fear memory in CRND8 mouse model of amyloidosis

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Hanna, Amanda, Iremonger, Kayleigh, Das, Pritam, Dickson, Dennis, Golde, Todd, Janus, Christopher·2012·Alzheimer's Research & Therapy
DOI 10.1186/alzrt124PMC PMC3506935
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Abstract

Introduction: The current pathological confirmation of the diagnosis of Alzheimer's disease (AD) is still based on postmortem identification of parenchymal amyloid beta (Aβ) plaques, intra-neuronal neurofibrillary tangles, and neuronal loss. The memory deficits that are present in the early stages of AD are linked to the dysfunction of structures in the entorhinal cortex and limbic system, especially the hippocampus and amygdala. Using the CRND8 transgenic mouse model of amyloidosis, which over-expresses a mutant human amyloid precursor protein (APP) gene, we evaluated hippocampus-dependent contextual and amygdala-dependent tone fear conditioned (FC) memory, and investigated the relationship between the fear memory indices and Aβ plaque burden. Methods: Mice were tested at three, six, and 12 months of age, which corresponds to early, mild, and severe Aβ plaque deposition, following a cross-sectional experimental design. We used a delay version of the fear conditioning paradigm in which tone stimulus was co-terminated with foot-shocks during exploration of the training chamber. The Aβ plaque burden was evaluated at each age after the completion of the behavioral tests. Results: CRDN8 mice showed context fear memory comparable to control mice at three and six months, but were significantly impaired at 12 months of age. In contrast, the tone fear memory was significantly impaired in the model at each age of testing. The Aβ plaque burden significantly increased with age, and was correlated with the overall impairment in context and tone fear memory in the CRND8 mice within the studied age. Conclusions: Our data extend previous studies showing that other APP mouse models exhibit impairment in fear conditioned memory, by demonstrating that this impairment is progressive and correlates well with an overall increase in Aβ burden. Also, the demonstrated greater sensitivity of the tone conditioning test in the identification of age dependent differences between CRND8 and control mice suggests that this paradigm might be particularly suitable in studies evaluating potential therapeutics related to memory improvement in mouse models of amyloidosis.

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  • Previous studies demonstrated age-dependent decline of conditioned fear memory in APP CRND8 mice.

    “In our previous studies, we also demonstrated age-dependent decline of conditioned fear memory in APP CRND8 mice [25].”

    From Normal cognition in transgenic BRI2-Aβ mice (2013) · cites this paper as [25]

  • 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 [25]

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Cited by

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Authors
Hanna, A., Iremonger, K., Das, P., Dickson, D., Golde, T., & Janus, C.
Affiliations
  • Mayo Clinic (US)
  • Roslin Institute (GB)
  • University of Florida (US)
Corresponding author
Janus, Christopher
ORCID
Venue
Alzheimer's Research & Therapy
Publisher
Springer Science and Business Media LLC
Published
2012-06-14
Volume
4
Issue
3
Pages
21-21
ISSN
1758-9193 (ISSN-L)
DOI
10.1186/alzrt124
PMC
PMC3506935
OpenAlex
W2095848871
Cited by
38
References
11
Citations by year
2026: 2 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 7
FWCI
3.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Alzheimer s Research & Therapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
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
Alzheimer's disease, amyloid plaques, amyloidosis, amyloid precursor protein, conditioned fear memory, contextual fear memory, age-related memory impairment, amygdala, hippocampus, transgenic mice

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