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

Kevin Huynh, Wei Ling Florence Lim, Corey Giles, Kaushala S. Jayawardana, Agus Salim, Natalie A. Mellett, Adam Alexander T. Smith, Gavriel Olshansky, Brian G. Drew, Pratishtha Chatterjee, Ian Martins, Simon M. Laws, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Colin L. Masters, Matthias Arnold, Kwangsik Nho, Andrew J. Saykin, Rebecca Baillie, Xianlin Han, Rima Kaddurah-Daouk (), Ralph N. Martins () and Peter J. Meikle ()
Additional contact information
Kevin Huynh: Baker Heart and Diabetes Institute
Wei Ling Florence Lim: Edith Cowan University
Corey Giles: Baker Heart and Diabetes Institute
Kaushala S. Jayawardana: Baker Heart and Diabetes Institute
Agus Salim: Baker Heart and Diabetes Institute
Natalie A. Mellett: Baker Heart and Diabetes Institute
Adam Alexander T. Smith: Baker Heart and Diabetes Institute
Gavriel Olshansky: Baker Heart and Diabetes Institute
Brian G. Drew: Baker Heart and Diabetes Institute
Pratishtha Chatterjee: Edith Cowan University
Ian Martins: Edith Cowan University
Simon M. Laws: Edith Cowan University
Ashley I. Bush: The University of Melbourne
Christopher C. Rowe: The University of Melbourne
Victor L. Villemagne: Austin Health
David Ames: National Ageing Research Institute
Colin L. Masters: The University of Melbourne
Matthias Arnold: Duke University
Kwangsik Nho: Indiana University School of Medicine
Andrew J. Saykin: Indiana University School of Medicine
Rebecca Baillie: Rosa & Co LLC
Xianlin Han: University of Texas Health Science Center at San Antonio
Rima Kaddurah-Daouk: Duke University
Ralph N. Martins: Edith Cowan University
Peter J. Meikle: Baker Heart and Diabetes Institute

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-020-19473-7

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