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Title: | Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer's disease. | Austin Authors: | Huynh, Kevin;Lim, Wei Ling Florence;Giles, Corey;Jayawardana, Kaushala S;Salim, Agus;Mellett, Natalie A;Smith, Adam Alexander T;Olshansky, Gavriel;Drew, Brian G;Chatterjee, Pratishtha;Martins, Ian;Laws, Simon M;Bush, Ashley I;Rowe, Christopher C ;Villemagne, Victor L ;Ames, David;Masters, Colin L ;Arnold, Matthias;Nho, Kwangsik;Saykin, Andrew J;Baillie, Rebecca;Han, Xianlin;Kaddurah-Daouk, Rima;Martins, Ralph N;Meikle, Peter J | Affiliation: | National Ageing Research Institute, Parkville, VIC, 3050, Australia Institute of Computational Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany Rosa & Co LLC, San Carlos, CA, USA School of Mathematics and Statistics, The University of Melbourne, Melbourne, VIC, 3010, Australia Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA Baker Heart and Diabetes Institute, Melbourne, VIC, Australia Monash University, Melbourne, VIC, 3800, Australia Department of Mathematics and Statistics, La Trobe University, Melbourne, VIC, Australia Melbourne School of Global and Population Health, The University of Melbourne, Melbourne, VIC, 3010, Australia School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia Department of Biomedical Sciences, Macquarie University, Sydney, NSW, Australia KaRa Institute of Neurological Disease, Sydney, NSW, Australia Cooperative research Centre (CRC) for Mental Health, Sydney, NSW, Australia Collaborative Genomics Group, School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia The Florey Department of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia Molecular Imaging and Therapy Medicine (University of Melbourne) School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Perth, WA, Australia Australian Alzheimer's Research Foundation, Nedlands, WA, Australia Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA Duke Institute of Brain Sciences, Duke University, Durham, NC, USA Department of Medicine, Duke University, Durham, NC, USA Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, IN, USA Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA |
Issue Date: | 10-Nov-2020 | Date: | 2020-11-10 | Publication information: | Nature Communications 2020; 11(1): 5698 | Abstract: | 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. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/25301 | DOI: | 10.1038/s41467-020-19473-7 | ORCID: | 0000-0001-6170-2207 0000-0002-8988-2147 0000-0003-4877-1958 0000-0002-2390-1501 0000-0002-4355-7082 0000-0001-8259-9069 0000-0002-4666-0923 0000-0002-1376-8532 0000-0003-3966-6320 0000-0002-8615-2413 0000-0003-1858-5732 0000-0002-2593-4665 |
Journal: | Nature Communications | PubMed URL: | 33173055 | Type: | Journal Article |
Appears in Collections: | Journal articles |
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