Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks.
Abstract
Apolipoprotein (apo) E4, one of three human apoE (h-apoE) isoforms, has been identified as a major genetic risk factor for Alzheimer's disease and for cognitive deficits associated with aging. However, the biological mechanisms involving apoE in learning and memory processes are unclear. A potential isoform-dependent role of apoE in cognitive processes was studied in human apoE targeted-replacement (TR) mice. These mice express either the human apoE3 or apoE4 gene under the control of endogenous murine apoE regulatory sequences, resulting in physiological expression of h-apoE in both a temporal and spatial pattern similar to humans. Male and female apoE3-TR, apoE4-TR, apoE-knockout and C57BL/6J mice (15-18 months) were tested with spatial memory and avoidance conditioning tasks. Compared to apoE3-TR mice, spatial memory in female apoE4-TR mice was impaired based on their poor performances in; (i) the probe test of the water-maze reference memory task, (ii) the water-maze working memory task and (iii) an active avoidance Y-maze task. Retention performance on a passive avoidance task was also impaired in apoE4-TR mice, but not in other genotypes. These deficits in both spatial and avoidance memory tasks may be related to the anatomical and functional abnormalities previously reported in the hippocampus and the amygdala of apoE4-TR mice. We conclude that the apoE4-TR mice provide an excellent model for understanding the mechanisms underlying apoE4-dependent susceptibility to cog…
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ApoE4 knock-in mice, particularly females, have deficits in spatial memory performance tests, compared to apoE3 mice.
“subsequent studies demonstrate that apoE4 knock-in mice, particularly females, have deficits in spatial memory performance tests, compared to apoE3 mice (Bour et al., 2008; Grootendorst et al., 2005).”
From Apolipoprotein E in Synaptic Plasticity and Alzheimer’s Disease: Potential Cellular and Molecular Mechanisms (2014) · cites this paper as Bour et al., 2008
Some phenotypic differences observed with apoE transgenic mouse models have been replicated with apoE knock-in mouse models.
“Some phenotypic differences observed with apoE transgenic mouse models have been replicated with apoE knock-in mouse models (Bour et al., 2008; Grootendorst et al., 2005; Trommer et al., 2004; Wang et al., 2005).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Bour et al., 2008
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- Authors
- Bour, A., Grootendorst, J., Vogel, E., Kelche, C., Dodart, J.-C., Bales, K., Moreau, P.-H., Sullivan, P. M., & Mathis, C.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Eli Lilly (United States) (US)
- Duke University (US)
- Corresponding author
- Mathis, Chantal
- ORCID
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2008-11
- Volume
- 193
- Issue
- 2
- Pages
- 174-182
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W2036092569
- Cited by
- 141
- References
- 6
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 8 · 2023: 2 · 2022: 8 · 2021: 15 · 2020: 10 · 2019: 8 · 2018: 8 · 2017: 9 · 2016: 13 · 2015: 7 · 2014: 6 · 2013: 14 · 2012: 9
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Centre National de la Recherche Scientifique
- 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
- APOE ε4, spatial memory, memory retention, avoidance conditioning, reference memory, working memory, sex differences, Alzheimer's disease risk, cognitive aging, hippocampus, amygdala, APOE isoforms, mouse model
- MeSH terms
- Animals, Apolipoproteins E, Avoidance Learning, Behavior, Animal, Cognition, Exploratory Behavior, Female, Genotype, Humans, Male, Memory, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Retention, Psychology, Spatial Behavior, Mice, Knockout, Maze Learning, Mice, Apolipoprotein E3, Apolipoprotein E4
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