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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.
Open accessAbstract
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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“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
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1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769 · cited 1×
“Ab oligomers are currently thought to be the key species involved in Ab toxicity (Lesne et al., 2006; Shankar et al., 2008; Walsh et al., 2002) but in the present study no change in expression of soluble oligomers was detected in the hippocampus of 3xTgAD mice on a high-fat diet at any time point.”
RetractedMorris water maze: procedures for assessing spatial and related forms of learning and memory
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“Ab oligomers are currently thought to be the key species involved in Ab toxicity (Lesne et al., 2006; Shankar et al., 2008; Walsh et al., 2002) but in the present study no change in expression of soluble oligomers was detected in the hippocampus of 3xTgAD mice on a high-fat diet at any time point.”
Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126
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“Ab oligomers are currently thought to be the key species involved in Ab toxicity (Lesne et al., 2006; Shankar et al., 2008; Walsh et al., 2002) but in the present study no change in expression of soluble oligomers was detected in the hippocampus of 3xTgAD mice on a high-fat diet at any time point.”
Neuropathological alterations in Alzheimer disease
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“In humans, the severity of AD-related neuropathology especially Ab plaque burden, does not always correlate with, or is predictive of, cognitive deficits, and memory impairments can occur in mouse AD models in advance of overt Ab plaque (and tangle) pathology (Billings et al., 2005; Oddo et al., 2003b; Serrano-Pozo et…”
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Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer's disease
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Metadata
- 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.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 35
- Issue
- 8
- Pages
- 1821-1832
- ISSN
- 0197-4580 (ISSN-L)
- 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
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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