Reference and working memory deficits in the 3xTg-AD mouse between 2 and 15-months of age: a cross-sectional study

Stevens, Leanne M.; Brown, Richard E.

doi:10.1016/j.bbr.2014.10.033

Cited by 92Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchMemory and Neural Mechanisms

Reference and working memory deficits in the 3xTg-AD mouse between 2 and 15-months of age: a cross-sectional study

Stevens, Leanne M., Brown, Richard E.·2015·Behavioural Brain Research

DOI 10.1016/j.bbr.2014.10.033

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Abstract

Impairments in working memory (WM) can predict the shift from mild cognitive impairment (MCI) to Alzheimer's disease (AD) and the rate at which AD progresses with age. The 3xTg-AD mouse model develops both Aβ plaques and neurofibrillary tangles, the neuro-pathological hallmarks of AD, by 6 months of age, but no research has investigated the age-related changes in WM in these mice. Using a cross-sectional design, we tested male and female 3xTg-AD and wildtype control (B6129SF2/J) mice between 2 and 15 months of age for reference and working memory errors in the 8-arm radial maze. The 3xTg-AD mice had deficits in both working and reference memory across the ages tested, rather than showing the predicted age-related memory deficits. Male 3xTg-AD mice showed more working and reference memory errors than females, but there were no sex differences in wildtype control mice. These results indicate that the 3xTg-AD mouse replicates the impairments in WM found in patients with AD. However, these mice show memory deficits as early as two months of age, suggesting that the genes underlying reference and working memory in these mice cause deficits from an early age. The finding that males were affected more than females suggests that more attention should be paid to sex differences in transgenic AD mice.

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The reduction in interhemispheric connectivity, particularly in the hippocampal formation at a prodromal stage in the 3xTg-AD model (2.0 months), could be related to alterations in working and reference memory.
“The reduction in interhemispheric connectivity, particularly in the hippocampal formation at a prodromal stage of the disease in the 3xTg-AD model (2.0 months) could be related to a previous report of alterations in working and reference memory (Stevens and Brown, 2015).”
From Early stage alterations in white matter and decreased functional interhemispheric hippocampal connectivity in the 3xTg mouse model of Alzheimer’s disease. (2019) · cites this paper as Stevens and Brown, 2015

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Additional file 1 of Differential effects of chronic immunosuppression on behavioral, epigenetic, and Alzheimer’s disease-associated markers in 3xTg-AD mice
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Authors: Stevens, L. M., & Brown, R. E.
Affiliations: Dalhousie University (CA)
Corresponding author: Brown, Richard E.
ORCID: Brown, Richard E.
Venue: Behavioural Brain Research
Publisher: Elsevier BV
Published: 2015-02
Volume: 278
Pages: 496-505
ISSN: 0166-4328 (ISSN-L)
DOI: 10.1016/j.bbr.2014.10.033
OpenAlex: W2028405984
Cited by: 92
References: 54
Citations by year: 2026: 2 · 2025: 10 · 2024: 6 · 2023: 11 · 2022: 8 · 2021: 8 · 2020: 7 · 2019: 13 · 2018: 9 · 2017: 7 · 2016: 7 · 2015: 4
FWCI: 3.99
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Behavioural Brain Research (publishedVersion)
PubMed (publishedVersion)
Funders: NSERC (A7741)
ASC
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, working memory, reference memory, age-related memory decline, sex differences, radial maze, amyloid plaques, neurofibrillary tangles, transgenic mouse model, mild cognitive impairment
MeSH terms: Age Factors, Aging, Alzheimer Disease, Animals, Cross-Sectional Studies, Disease Models, Animal, Female, Male, Memory Disorders, Memory, Short-Term, Mice, Transgenic, Sex Factors, Statistics, Nonparametric, Maze Learning, Mice

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Reference and working memory deficits in the 3xTg-AD mouse between 2 and 15-months of age: a cross-sectional study

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