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Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease
Authors
David Ames
Matthias Arnold
+23 more
Rebecca Baillie
Ashley I. Bush
Pratishtha Chatterjee
Brian G. Drew
Corey Giles
Xianlin Han
Kevin Huynh
Kaushala S. Jayawardana
Rima Kaddurah-Daouk
Simon M. Laws
Wei Ling Florence Lim
Ian Martins
Ralph N. Martins
Colin L. Masters
Peter J. Meikle
Natalie A. Mellett
Kwangsik Nho
Gavriel Olshansky
Christopher C. Rowe
Agus Salim
Andrew J. Saykin
Adam Alexander T. Smith
Victor L. Villemagne
Publication date
1 January 2020
Publisher
Edith Cowan University, Research Online, Perth, Western Australia
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Abstract
© 2020, The Author(s). 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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