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Neth, B.J.* ; Huynh, K.* ; Giles, C.* ; Wang, T.* ; Mellett, N.A.* ; Duong, T.* ; Blach, C.* ; Schimmel, L.* ; Register, T.C.* ; Blennow, K.* ; Zetterberg, H.* ; Batra, R.* ; Schweickart, A.* ; Dilmore, A.H.* ; Martino, C.* ; Arnold, M. ; Krumsiek, J.* ; Han, X.* ; Dorrestein, P.C.* ; Knight, R.* ; Meikle, P.J.* ; Craft, S.* ; Kaddurah-Daouk, R.*

Consuming a modified Mediterranean ketogenic diet reverses the peripheral lipid signature of Alzheimer's disease in humans.

Commun. Med. 5:11 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
BACKGROUND: Alzheimer's disease (AD) is a major neurodegenerative disorder with significant environmental factors, including diet and lifestyle, influencing its onset and progression. Although previous studies have suggested that certain diets may reduce the incidence of AD, the underlying mechanisms remain unclear. METHOD: In this post-hoc analysis of a randomized crossover study of 20 elderly adults, we investigated the effects of a modified Mediterranean ketogenic diet (MMKD) on the plasma lipidome in the context of AD biomarkers, analyzing 784 lipid species across 47 classes using a targeted lipidomics platform. RESULTS: Here we identified substantial changes in response to MMKD intervention, aside from metabolic changes associated with a ketogenic diet, we identified a a global elevation across all plasmanyl and plasmenyl ether lipid species, with many changes linked to clinical and biochemical markers of AD. We further validated our findings by leveraging our prior clinical studies into lipid related changeswith AD (n = 1912), and found that the lipidomic signature with MMKD was inversely associated with the lipidomic signature of prevalent and incident AD. CONCLUSIONS: Intervention with a MMKD was able to alter the plasma lipidome in ways that contrast with AD-associated patterns. Given its low risk and cost, MMKD could be a promising approach for prevention or early symptomatic treatment of AD.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Beta-oxidation; Mitochondrial; Biosynthesis; Metabolism; Insights; Models; Health; Decade; Scale
ISSN (print) / ISBN 2730-664X
e-ISSN 2730-664X
Quellenangaben Volume: 5, Issue: 1, Pages: , Article Number: 11 Supplement: ,
Publisher Springer
Publishing Place Campus, 4 Crinan St, London, N1 9xw, England
Non-patent literature Publications
Reviewing status Peer reviewed
Grants National Institute of Aging of the National Institutes of Health
National Health and Medical Research Council (NHMRC)
FNIH
NIA
Alzheimer's Gut Microbiome Project (AGMP) or the Alzheimer's Disease Metabolomics Consortium (ADMC)
Swedish State Support for Clinical Research (ALFGBG)
Swedish Research Council
National Center for Advancing Translational Sciences (NCATS) through National Institutes of Health
Roena B. Kulynych Center for Memory and Cognition Research
Hartman Family Foundation
Alzheimer's association
European Union

UK Dementia Research Institute at UCL
National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre
European Union Joint Programme - Neurodegenerative Disease Research
Stiftelsen foer Gamla Tjaenarinnor, Hjaernfonden, Sweden
Erling-Persson Family Foundation
Olav Thon Foundation
Bluefield Project
AD Strategic Fund and the Alzheimer's Association
Alzheimer Drug Discovery Foundation (ADDF), USA
Swedish State Support for Clinical Research
Wake Forest Alzheimer's Disease Research Center (WFADRC)