Cited by 107Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchMemory and Neural Mechanisms

Evidence for early cognitive impairment related to frontal cortex in the 5xFAD mouse model of Alzheimer’s disease.

Girard, Stéphane D., Baranger, Kévin, Gauthier, Cyrielle, Jacquet, Marlyse, Bernard, Anne, Escoffier, Guy, Marchetti, Evelyne, Khrestchatisky, Michel +2 more·2013·Journal 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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Crossref · 10.3233/jad-2012-120982

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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.
Venue
Journal of Alzheimer s Disease
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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