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.
GrantsNational 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)