A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer's disease
Open accessAbstract
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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Several clinical studies have shown a positive effect of a ketogenic diet on patients with AD or mild cognitive impairment (MCI), consistent with preclinical results.
“Several clinical studies have shown a positive effect of a ketogenic diet on patients with AD or mild cognitive impairment (MCI), consistent with preclinical results [87–91] (Table 1).”
From Role of diet and its effects on the gut microbiome in the pathophysiology of mental disorders (2022) · cites this paper as [89]
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- 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
- Published
- 2005-10-17
- Volume
- 2
- Issue
- 1
- Pages
- 28-28
- ISSN
- 1743-7075 (ISSN-L)
- 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
- gold
- doi.org
- 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 › Diet and metabolism studies
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Physiology › 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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