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

Author

Listed:
  • Kevin Huynh

    (Baker Heart and Diabetes Institute
    Monash University)

  • Wei Ling Florence Lim

    (Edith Cowan University
    Cooperative research Centre (CRC) for Mental Health)

  • Corey Giles

    (Baker Heart and Diabetes Institute)

  • Kaushala S. Jayawardana

    (Baker Heart and Diabetes Institute)

  • Agus Salim

    (Baker Heart and Diabetes Institute
    La Trobe University
    The University of Melbourne
    The University of Melbourne)

  • 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
    Monash University)

  • Pratishtha Chatterjee

    (Edith Cowan University
    Macquarie University
    KaRa Institute of Neurological Disease)

  • Ian Martins

    (Edith Cowan University
    Cooperative research Centre (CRC) for Mental Health)

  • Simon M. Laws

    (Edith Cowan University
    Edith Cowan University
    Curtin University)

  • Ashley I. Bush

    (The University of Melbourne)

  • Christopher C. Rowe

    (The University of Melbourne
    Austin Health)

  • Victor L. Villemagne

    (Austin Health
    The University of Melbourne)

  • David Ames

    (National Ageing Research Institute)

  • Colin L. Masters

    (The University of Melbourne)

  • Matthias Arnold

    (Duke University
    German Research Center for Environmental Health)

  • Kwangsik Nho

    (Indiana University School of Medicine
    Indiana University School of Medicine
    Indiana University School of Medicine)

  • Andrew J. Saykin

    (Indiana University School of Medicine
    Indiana University School of Medicine
    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
    Duke University
    Duke University)

  • Ralph N. Martins

    (Edith Cowan University
    Cooperative research Centre (CRC) for Mental Health
    Macquarie University
    KaRa Institute of Neurological Disease)

  • Peter J. Meikle

    (Baker Heart and Diabetes Institute
    Monash University)

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.

Suggested Citation

  • 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 & Ia, 2020. "Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19473-7
    DOI: 10.1038/s41467-020-19473-7
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    Cited by:

    1. Laura K. Hamilton & Gaël Moquin-Beaudry & Chenicka L. Mangahas & Federico Pratesi & Myriam Aubin & Anne Aumont & Sandra E. Joppé & Alexandre Légiot & Annick Vachon & Mélanie Plourde & Catherine Mounie, 2022. "Stearoyl-CoA Desaturase inhibition reverses immune, synaptic and cognitive impairments in an Alzheimer’s disease mouse model," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Gemma Cadby & Corey Giles & Phillip E. Melton & Kevin Huynh & Natalie A. Mellett & Thy Duong & Anh Nguyen & Michelle Cinel & Alex Smith & Gavriel Olshansky & Tingting Wang & Marta Brozynska & Mike Ino, 2022. "Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Oana A. Zeleznik & Jae H. Kang & Jessica Lasky-Su & A. Heather Eliassen & Lisa Frueh & Clary B. Clish & Bernard A. Rosner & Tobias Elze & Pirro Hysi & Anthony Khawaja & Janey L. Wiggs & Louis R. Pasqu, 2023. "Plasma metabolite profile for primary open-angle glaucoma in three US cohorts and the UK Biobank," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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