Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer’s disease (AD). Lipids are complex molecules comprising many isomeric and isobaric species, necessitating detailed analysis to enable interpretation of biological significance. Our expanded targeted lipidomics platform (569 species across 32 classes) allows for detailed lipid separation and characterisation. In this study we examined peripheral samples of two cohorts (AIBL, n = 1112 and ADNI, n = 800). We are able to identify concordant peripheral signatures associated with prevalent AD arising from lipid pathways including; ether lipids, sphingolipids (notably GM3 gangliosides) and lipid classes previously associated with cardiometabolic disease (phosphatidylethanolamine and triglycerides). We subsequently identified similar lipid signatures in both cohorts with future disease. Lastly, we developed multivariate lipid models that improved classification and prediction. Our results provide a holistic view between the lipidome and AD using a comprehensive approach, providing targets for further mechanistic investigation.
FörderungenEdith Cowan University (ECU), Mental Health Research institute NCI National Institute on Aging NIA's national initiatives AMP-AD Alzheimer's Disease Metabolomics Consortium NIA National Ageing Research Institute (NARI) CogState Ltd National Health and Medical Research Council (NHMRC) Dementia Collaborative Research Centres program (DCRC2) Science and Industry Endowment Fund (SIEF) Cooperative Research Centre (CRC) CRC Program Australian Government Initiative Victorian Government's Operational Infrastructure Support Program Dementia Australia Research Foundation Scholarship National Health and Medical Research Council of Australia National Institute on Aging (NIA) Qatar National Research Fund National Institutes of Health Merck Co., Inc. Meso Scale Diagnostics, LLC Novartis Pharmaceuticals Corporation Pfizer Inc. Piramal Imaging Takeda Pharmaceutical Company Canadian Institutes of Health Research ADNI clinical sites in Canada Foundation for the National Institutes of Health Northern California Institute for Research and Education Laboratory for Neuro Imaging at the University of Southern California Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu) Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity IXICO Ltd Fujirebio National Institute of Biomedical Imaging and Bioengineering Alzheimer's Association Alzheimer's Drug Discovery Foundation Araclon Biotech Biogen Bristol-Myers Squibb Company CereSpir, Inc. Cogstate Elan Pharmaceuticals, Inc. Eli Lilly and Company EuroImmun F. Hoffmann-La Roche Ltd Alzheimer's Disease Metabolomics Consortium (ADMC)