Journal
NATURE COMMUNICATIONS
Volume 11, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-020-19473-7
Keywords
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Categories
Funding
- Edith Cowan University (ECU), Mental Health Research institute
- 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 [:20100104]
- 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)
- NIA
- Alzheimer's Disease Metabolomics Consortium
- NIA's national initiatives AMP-AD [R01 AG046171, RF1 AG051550, RF1 AG057452, 3U01 AG024904-09S4]
- NCI [P30 AG10133, R01 AG19771, R01 LM012535, R03 AG054936, R01 AG061788, K01 AG049050, R01 CA129769]
- National Institute on Aging
- Qatar National Research Fund [NPRP8-061-3-011, NLM R01 LM012535, NIA R03AG054936]
- National Institutes of Health [U01 AG024904]
- 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
- Fujirebio
- IXICO Ltd
- Johnson AMP
- Johnson Pharmaceutical Research AMP
- Development LLC
- Lumosity
- 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)
- Alzheimer's Disease Metabolomics Consortium (ADMC)
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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 GM(3) 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. The onset and pathology of Alzheimer's disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma lipidome with AD and the future onset of AD.
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