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^*

^*Corresponding author for this work

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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
Article number	5698
Pages (from-to)	1-11
Number of pages	11
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-19473-7
Publication status	Published - 1 Dec 2020

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Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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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), 1-11. Article 5698. https://doi.org/10.1038/s41467-020-19473-7

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title = "Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer{\textquoteright}s disease",

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.}",

note = "Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.",

year = "2020",

month = dec,

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doi = "10.1038/s41467-020-19473-7",

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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, pp. 1-11. https://doi.org/10.1038/s41467-020-19473-7

TY - JOUR

T1 - Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease

AU - Huynh, Kevin

AU - Lim, Wei Ling Florence

AU - Giles, Corey

AU - Jayawardana, Kaushala S.

AU - Salim, Agus

AU - Mellett, Natalie A.

AU - Smith, Adam Alexander T.

AU - Olshansky, Gavriel

AU - Drew, Brian G.

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.

N1 - Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2020/12/1

Y1 - 2020/12/1

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.

AB - 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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U2 - 10.1038/s41467-020-19473-7

DO - 10.1038/s41467-020-19473-7

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C2 - 33173055

AN - SCOPUS:85095778276

SN - 2041-1723

VL - 11

SP - 1

EP - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 5698

ER -

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

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