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Onset of hippocampus-dependent memory impairments in 5XFAD transgenic mouse model of Alzheimer’s disease
Abstract
The 5XFAD mice are an early‐onset transgenic model of Alzheimer's disease (AD) in which amyloid plaques are first observed between two and four months of age in the cortical layer five and in the subiculum of the hippocampal formation. Although cognitive alterations have been described in these mice, there are no studies that focused on the onset of hippocampus‐dependent memory deficits, which are a hallmark of the prodromal stage of AD. To identify when the first learning and memory impairments appear, 5XFAD mice of two, four, and six months of age were compared with their respective wild‐type littermates using the olfactory tubing maze, which is a very sensitive hippocampal‐dependent task. Deficits in learning and memory started at four months with a substantial increase at six months of age while no olfactory impairments were observed. The volumetric study using magnetic resonance imaging of the whole brain and specific areas (olfactory bulb, striatum, and hippocampus) did not reveal neuro‐anatomical difference. Slight memory deficits appeared at 4 months of age in correlation with an increased astrogliosis and amyloid plaque formation. This early impairment in learning and memory related to the hippocampal dysfunction is particularly suited to assess preclinical therapeutic strategies aiming to delay or suppress the onset of AD. © 2014 Wiley Periodicals, Inc.
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“Interestingly, behavioral and memory deficits do not typically begin to show significant differences in 5xFAD animals until at least 5-7 months of age (Girard et al., 2014; Ohno, 2009).”
From LC3-Associated Endocytosis Facilitates β-Amyloid Clearance and Mitigates Neurodegeneration in Murine Alzheimer’s Disease (2019) · cites this paper as Girard et al., 2014
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Metadata
- Authors
- Girard, S. D., Jacquet, M., Baranger, K., Migliorati, M., Escoffier, G., Bernard, A., Khrestchatisky, M., Féron, F., Rivera, S., Roman, F. S., & Marchetti, E.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Aix Marseille Université, CNRS, NICN, UMR7259 Marseille France
- Corresponding author
- Roman, François S.
- ORCID
- Venue
- Hippocampus
- Publisher
- Wiley
- Published
- 2014-03-14
- Volume
- 24
- Issue
- 7
- Pages
- 762-772
- ISSN
- 1050-9631 (ISSN-L)
- 1098-1063
- OpenAlex
- W1532925865
- Cited by
- 119
- References
- 42
- Citations by year
- 2026: 13 · 2025: 7 · 2024: 13 · 2023: 13 · 2022: 22 · 2021: 14 · 2020: 5 · 2019: 9 · 2018: 8 · 2017: 5 · 2016: 3 · 2015: 3 · 2014: 4
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hippocampus (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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
- 5xFAD mice, Alzheimer's disease, hippocampal-dependent memory, learning and memory impairment, prodromal Alzheimer's disease, amyloid plaques, astrocyte activation, olfactory bulb, hippocampal dysfunction
- MeSH terms
- Alzheimer Disease, Animals, Astrocytes, Corpus Striatum, Gliosis, Hippocampus, Learning Disabilities, Magnetic Resonance Imaging, Male, Memory Disorders, Mice, Transgenic, Olfactory Bulb, Organ Size, Smell, Amyloid beta-Protein Precursor, Point Mutation, Age of Onset, Maze Learning, Mice, Presenilin-1, Plaque, Amyloid
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