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; Peter J. Meikle

doi:10.1038/s41467-020-19473-7

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. SaykinRebecca Baillie, Xianlin Han, Rima Kaddurah-Daouk, Ralph N. Martins, Peter J. Meikle

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72 Scopus citations

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.

Original language	English (US)
Article number	5698
Journal	Nature communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-19473-7
State	Published - Dec 2020

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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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., ... Meikle, P. J. (2020). Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease. Nature communications, 11(1), Article 5698. https://doi.org/10.1038/s41467-020-19473-7

Huynh, K, Lim, WLF, Giles, C, Jayawardana, KS, Salim, A, Mellett, NA, Smith, AAT, Olshansky, G, Drew, BG, Chatterjee, P, Martins, I, Laws, SM, Bush, AI, Rowe, CC, Villemagne, VL, Ames, D, Masters, CL, Arnold, M, Nho, K, Saykin, AJ, Baillie, R, Han, X, Kaddurah-Daouk, R, Martins, RN & Meikle, PJ 2020, 'Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease', Nature communications, vol. 11, no. 1, 5698. https://doi.org/10.1038/s41467-020-19473-7

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abstract = "Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer{\textquoteright}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.",

author = "Kevin Huynh and Lim, {Wei Ling Florence} and Corey Giles and Jayawardana, {Kaushala S.} and Agus Salim and Mellett, {Natalie A.} and Smith, {Adam Alexander T.} and Gavriel Olshansky and Drew, {Brian G.} and Pratishtha Chatterjee and Ian Martins and Laws, {Simon M.} and Bush, {Ashley I.} and Rowe, {Christopher C.} and Villemagne, {Victor L.} and David Ames and Masters, {Colin L.} and Matthias Arnold and Kwangsik Nho and Saykin, {Andrew J.} and Rebecca Baillie and Xianlin Han and Rima Kaddurah-Daouk and Martins, {Ralph N.} and Meikle, {Peter J.}",

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AU - Smith, Adam Alexander T.

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AU - Chatterjee, Pratishtha

AU - Martins, Ian

AU - Laws, Simon M.

AU - Bush, Ashley I.

AU - Rowe, Christopher C.

AU - Villemagne, Victor L.

AU - Ames, David

AU - Masters, Colin L.

AU - Arnold, Matthias

AU - Nho, Kwangsik

AU - Saykin, Andrew J.

AU - Baillie, Rebecca

AU - Han, Xianlin

AU - Kaddurah-Daouk, Rima

AU - Martins, Ralph N.

AU - Meikle, Peter J.

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N2 - 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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Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease

Abstract

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