High-fat diet-induced memory impairment in triple-transgenic Alzheimer’s disease (3xTgAD) mice is independent of changes in amyloid and tau pathology.

Knight, Elysse M.; Martins, Isaura V.A.; Gümüsgöz, Sarah; Allan, Stuart M.; Lawrence, Catherine B.

doi:10.1016/j.neurobiolaging.2014.02.010

Cited by 232Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeurological Disease Mechanisms and Treatments

High-fat diet-induced memory impairment in triple-transgenic Alzheimer’s disease (3xTgAD) mice is independent of changes in amyloid and tau pathology.

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Knight, Elysse M., Martins, Isaura V.A., Gümüsgöz, Sarah, Allan, Stuart M., Lawrence, Catherine B.·2014·Neurobiology of Aging

DOI 10.1016/j.neurobiolaging.2014.02.010PMC PMC4024197

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Abstract

Obesity and consumption of a high-fat diet are known to increase the risk of Alzheimer's disease (AD). Diets high in fat also increase disease neuropathology and/or cognitive deficits in AD mouse models. However, the effect of a high-fat diet on both the neuropathology and memory impairments in the triple-transgenic mouse model of AD (3xTgAD) is unknown. Therefore, groups of 2-month-old male 3xTgAD and control (non-Tg) mice were maintained on a high-fat or control diet and memory was assessed at the age of 3-4, 7-8, 11-12, and 15-16 months using a series of behavioral tests. A comparable increase in body weight was observed in non-Tg and 3xTgAD mice after high-fat feeding at all ages tested but a significantly greater increase in epididymal adipose tissue was observed in 3xTgAD mice at the age of 7-8, 11-12, and 15-16 months. A high-fat diet caused memory impairments in non-Tg control mice as early as the age of 3-4 months. In 3xTgAD mice, high-fat consumption led to a reduction in the age of onset and an increase in the extent of memory impairments. Some of these effects of high-fat diet on cognition in non-Tg and 3xTgAD mice were transient, and the age at which cognitive impairment was detected depended on the behavioral test. The effect of high-fat diet on memory in the 3xTgAD mice was independent of changes in AD neuropathology as no significant differences in (plaques, oligomers) or tau neuropathology were observed. An acute increase in microglial activation was seen in high-fat fed 3xTgAD mice at the age of 3-4 months but in non-Tg control mice microglial activation was not observed until the age of 15-16 months. These data indicate therefore that a high-fat diet has rapid and long-lasting negative effects on memory in both control and AD mice that are associated with neuroinflammation, but independent of changes in beta amyloid and tau neuropathology in the AD mice.

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Addition of a high fat/high sugar diet exacerbates Alzheimer's disease phenotypes in mouse models relevant to early-onset AD.
“Also, the addition of an HFD exacerbated AD phenotypes in mouse models relevant to early-onset AD (Knight et al., 2014; Jones et al., 2019; Bracko et al., 2020; Robison et al., 2020; Jones et al., 2021).”
From Plcg2M28L Interacts With High Fat/High Sugar Diet to Accelerate Alzheimer’s Disease-Relevant Phenotypes in Mice (2022) · cites this paper as Knight et al., 2014
The Discussion (page unavailable) reports that a high-fat diet worsened memory deficits in 3xTgAD mice, supporting the high-fat-diet part of the citing sentence. The Methods describe the diet as high-fat, not high-fat/high-sugar; the quoted claim’s added sugar qualifier is unsupported. The Discussion also reports no increase in amyloid or tau deposition, so the exacerbation shown is cognitive rather than neuropathological. (LLM, conf=0.84)
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P1‐154: Effect of high fat diet on memory in the 3xTgAD triple transgenic model of Alzheimer's disease
Knight, E. M., Allan, S. M., & Lawrence, C. B. (2010) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2010.05.704
Self-citation
Maternal High-Fat Diet Worsens Memory Deficits in the Triple-Transgenic (3xTgAD) Mouse Model of Alzheimer’s Disease
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Self-citation
Effect of a high fat diet on a mouse model of Alzheimer's disease
Lawrence, C. B., Allan, S. M., & Knight, E. M. (2011) · OpenGrey (Institut de l'Information Scientifique et Technique)
Self-citation
Effect of high-fat diet on cognitive impairment in triple-transgenic mice model of Alzheimer's disease
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Mitochondrial Abnormalities and Synaptic Loss Underlie Memory Deficits Seen in Mouse Models of Obesity and Alzheimer’s Disease
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Self-citation

Authors: Knight, E. M., Martins, I. V. A., Gümüsgöz, S., Allan, S. M., & Lawrence, C. B.
Affiliations: University of Manchester (GB)
Corresponding author: Lawrence, Catherine B.
ORCID: Knight, Elysse M.
Allan, Stuart M.
Lawrence, Catherine B.
Venue: Neurobiology of Aging
Publisher: Elsevier BV
Published: 2014-08
Volume: 35
Issue: 8
Pages: 1821-1832
ISSN: 0197-4580 (ISSN-L)
DOI: 10.1016/j.neurobiolaging.2014.02.010
PMC: PMC4024197
OpenAlex: W1994083528
Cited by: 232
References: 56
Citations by year: 2026: 11 · 2025: 14 · 2024: 14 · 2023: 19 · 2022: 23 · 2021: 20 · 2020: 21 · 2019: 26 · 2018: 24 · 2017: 18 · 2016: 30 · 2015: 7 · 2014: 5
FWCI: 13.33
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/3.0/ (vor)
Locations: Neurobiology of Aging (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Research Explorer (The University of Manchester) (submittedVersion)
Funders: Medical Research Council
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 › Neurology › Neurological Disease Mechanisms and Treatments
Keywords: high-fat diet, Alzheimer's disease, 3xTg-AD mice, memory impairment, obesity, amyloid plaques, tau pathology, microglial activation, neuroinflammation, adipose tissue, cognitive aging
MeSH terms: Adipose Tissue, Alzheimer Disease, Animals, Brain, Cognition, Disease Models, Animal, Epididymis, Male, Memory, Mice, Transgenic, Risk, Amyloid beta-Peptides, tau Proteins, Mice, Diet, High-Fat

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High-fat diet-induced memory impairment in triple-transgenic Alzheimer’s disease (3xTgAD) mice is independent of changes in amyloid and tau pathology.

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