Evidence for early cognitive impairment related to frontal cortex in the 5xFAD mouse model of Alzheimer’s disease.
Abstract
The frontal cortex is a brain structure that plays an important role in cognition and is known to be affected in Alzheimer's disease (AD) in humans. Over the past years, transgenic mouse models have been generated to recapitulate the main features of this disease, including cognitive impairments. This study investigates frontal cortex dependent learning abilities in one of the most early-onset transgenic murine model of AD, the 5XFAD mice. We compared frontal performance of 2-, 4-, and 6-month-old 5XFAD mice with their wild-type littermates using a newly developed automated device, the olfactory H-maze, in which mice have to discover three different rules consecutively according to the delayed reaction paradigm. We report early cognitive deficits related to frontal cortex appearing in 4-month-old 5XFAD mice before hippocampal-dependent learning and memory impairment, in relation with neuropathologic processes such as strong gliosis and emerging amyloid plaques. The present results demonstrate that the olfactory H-maze is a very sensitive and simple experimental paradigm that allows assessment of frontal functions in transgenic mice and should be useful to test pre-clinical therapeutic approaches to alter the course of AD.
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The 5xFAD transgenic mice have been acknowledged as a useful model for better understanding the pathogenesis of human AD.
“The 5xFAD transgenic mice have been acknowledged as a useful model for better understanding the pathogenesis of human AD (Girard et al., 2013).”
From Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging (2022) · cites this paper as Girard et al., 2013
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- Authors
- Girard, S. D., Baranger, K., Gauthier, C., Jacquet, M., Bernard, A., Escoffier, G., Marchetti, E., Khrestchatisky, M., Rivera, S., & Roman, F. S.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Roman, François S.
- ORCID
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2013-01-10
- Volume
- 33
- Issue
- 3
- Pages
- 781-796
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1533260153
- Cited by
- 107
- References
- 46
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 12 · 2023: 6 · 2022: 6 · 2021: 12 · 2020: 12 · 2019: 7 · 2018: 6 · 2017: 2 · 2016: 5 · 2015: 5 · 2014: 9 · 2013: 6
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Aix-Marseille Université
- Agence Nationale de la Recherche
- European Regional Development Fund
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- Alzheimer's disease, 5xFAD mice
- MeSH terms
- Age Factors, Alzheimer Disease, Analysis of Variance, Animals, Olfaction Disorders, Frontal Lobe, Glial Fibrillary Acidic Protein, Humans, Magnetic Resonance Imaging, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Reaction Time, Amyloid beta-Protein Precursor, Maze Learning, Mice, Presenilin-1, Cognitive Dysfunction
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