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Huynh, K.* ; Lim, W.L.F.* ; Giles, C.* ; Jayawardana, K.S.* ; Salim, A.* ; Mellett, N.A.* ; Smith, A.A.T.* ; Olshansky, G.* ; Drew, B.G.* ; Chatterjee, P.* ; Martins, I.* ; Laws, S.M.* ; Bush, A.I.* ; Rowe, C.C.* ; Villemagne, V.L.* ; Ames, D.* ; Masters, C.L.* ; Arnold, M. ; Nho, K.* ; Saykin, A.J.* ; Baillie, R.* ; Han, X.* ; Kaddurah-Daouk, R.* ; Meikle, P.J.*

Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease.

Nat. Commun. 11:5698 (2020)

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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 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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Plasmalogen Deficiency; Diabetes-mellitus; Dementia; Phospholipids; Risk; Biosynthesis; Aggregation; Synthase; Tau

ISSN (print) / ISBN 2041-1723

e-ISSN 2041-1723

Journal Nature Communications

Quellenangaben Volume: 11, Issue: 1, Article Number: 5698

Publisher Nature Publishing Group

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Computational Biology (ICB)

Grants Edith 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)