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Cited by 307Diet and metabolism studiesAlzheimer's disease research and treatmentsDietary Effects on Health

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A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer's disease

Open access
Van der Auwera, Ingrid, Wera, Stefaan, Van Leuven, Fred, Henderson, Samuel T·2005·Nutrition & Metabolism
DOI 10.1186/1743-7075-2-28PMC PMC1282589
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Abstract

Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that primarily strikes the elderly. Studies in both humans and animal models have linked the consumption of cholesterol and saturated fats with amyloid-β (Aβ) deposition and development of AD. Yet, these studies did not examine high fat diets in combination with reduced carbohydrate intake. Here we tested the effect of a high saturated fat/low carbohydrate diet on a transgenic mouse model of AD. Results: Starting at three months of age, two groups of female transgenic mice carrying the "London" APP mutation (APP/V717I) were fed either, a standard diet (SD) composed of high carbohydrate/low fat chow, or a ketogenic diet (KD) composed of very low carbohydrate/high saturated fat chow for 43 days. Animals fed the KD exhibited greatly elevated serum ketone body levels, as measured by β-hydroxybutyrate (3.85 ± 2.6 mM), compared to SD fed animals (0.29 ± 0.06 mM). In addition, animals fed the KD lost body weight (SD 22.2 ± 0.6 g vs. KD 17.5 ± 1.4 g, p = 0.0067). In contrast to earlier studies, the brief KD feeding regime significantly reduced total brain Aβ levels by approximately 25%. Despite changes in ketone levels, body weight, and Aβ levels, the KD diet did not alter behavioral measures. Conclusion: Previous studies have suggested that diets rich in cholesterol and saturated fats increased the deposition of Aβ and the risk of developing AD. Here we demonstrate that a diet rich in saturated fats and low in carbohydrates can actually reduce levels of Aβ. Therefore, dietary strategies aimed at reducing Aβ levels should take into account interactions of dietary components and the metabolic outcomes, in particular, levels of carbohydrates, total calories, and presence of ketone bodies should be considered.

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Crossref · 10.1186/1743-7075-2-28

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Figures

Figure 1 Average weight in grams of each group during the course of the experiment. Blue squares represent standard diet (SD) group. Red circles represent ketogenic diet (KD) group. Error bars represent standard error of the mean. Days signify time in days from start of diet change. Animals on KD lost weight. To mitigate weight loss and improve feeding a small amount of SD chow was mixed with KD chow during the second week and then removed on the third week, see methods.
Figure 1 Average weight in grams of each group during the course of the experiment. Blue squares represent standard diet (SD) group. Red circles represent ketogenic diet (KD) group. Error bars represent standard error of the mean. Days signify time in days from start of diet change. Animals on KD lost weight. To mitigate weight loss and improve feeding a small amount of SD chow was mixed with KD chow during the second week and then removed on the third week, see methods.CC BY · PubMed Central
Figure 2 Ketogenic diet induces ketone bodies production. Standard diet (SD) group shown in blue, ketogenic diet (KD) group shown in red, error bars represent standard error of the mean. Serum β-hydroxybutyrate (BHB) levels in mM. * indicates p < 0.05 between KD and SD group. Days signify time in days from start of diet change. Serum β-hydroxybutyrate levels were significantly elevated in KD group at all time points after day 0. Bar indicates period of mixed chow for KD group.
Figure 2 Ketogenic diet induces ketone bodies production. Standard diet (SD) group shown in blue, ketogenic diet (KD) group shown in red, error bars represent standard error of the mean. Serum β-hydroxybutyrate (BHB) levels in mM. * indicates p < 0.05 between KD and SD group. Days signify time in days from start of diet change. Serum β-hydroxybutyrate levels were significantly elevated in KD group at all time points after day 0. Bar indicates period of mixed chow for KD group.CC BY · PubMed Central
Figure 3 Ketogenic diet reduces Aβ40 and Aβ42. Aβ levels as ng/g of brain tissue. Standard diet (SD) group shown in blue, ketogenic diet (KD) group shown in red, error bars represent standard error of the mean. SD chow Aβ40 1.72 ± 0.12 ng/g vs. KD chow Aβ40 1.28 ± 0.09 ng/g, p= 0.012. SD chow Aβ42 0.88 ± 0.05 ng/g vs. KD chow Aβ42 0.71 ± 0.0.4 ng/g, p = 0.016.
Figure 3 Ketogenic diet reduces Aβ40 and Aβ42. Aβ levels as ng/g of brain tissue. Standard diet (SD) group shown in blue, ketogenic diet (KD) group shown in red, error bars represent standard error of the mean. SD chow Aβ40 1.72 ± 0.12 ng/g vs. KD chow Aβ40 1.28 ± 0.09 ng/g, p= 0.012. SD chow Aβ42 0.88 ± 0.05 ng/g vs. KD chow Aβ42 0.71 ± 0.0.4 ng/g, p = 0.016.CC BY · PubMed Central

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Metadata

Authors
Van der Auwera, I., Wera, S., Van Leuven, F., & Henderson, S. T.
Affiliations
KU Leuven (BE)
Corresponding author
Henderson, Samuel T
Venue
Nutrition & Metabolism
Publisher
Springer Science and Business Media LLC
Published
2005-10-17
Volume
2
Issue
1
Pages
28-28
ISSN
1743-7075 (ISSN-L)
DOI
10.1186/1743-7075-2-28
PMC
PMC1282589
OpenAlex
W2109680432
Cited by
307
References
40
Citations by year
2026: 8 · 2025: 12 · 2024: 12 · 2023: 22 · 2022: 36 · 2021: 23 · 2020: 36 · 2019: 24 · 2018: 15 · 2017: 15 · 2016: 12 · 2015: 12 · 2014: 15 · 2013: 11 · 2012: 13
FWCI
3.61
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nutrition & Metabolism (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Health Sciences › Medicine › Physiology (medical) › Diet and metabolism studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
Keywords
ketogenic diet, Alzheimer's disease, amyloid-beta, Aβ40, amyloid-beta 42, high saturated fat diet, low-carbohydrate diet, ketone bodies, beta-hydroxybutyrate, dietary intervention, cholesterol, weight loss

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