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

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    Author
    Huynh, K; Lim, WLF; Giles, C; Jayawardana, KS; Salim, A; Mellett, NA; Smith, AAT; Olshansky, G; Drew, BG; Chatterjee, P; ...
    Date
    2020-11-10
    Source Title
    Nature Communications
    Publisher
    NATURE RESEARCH
    University of Melbourne Author/s
    Ames, David; Masters, Colin; Meikle, Peter; Bush, Ashley; Rowe, Christopher; Villemagne, Victor; Salim, Agus; Huynh, Kevin; Smith, Adam; Giles, Corey
    Affiliation
    Psychiatry
    Florey Department of Neuroscience and Mental Health
    Bio21
    Medicine and Radiology
    Melbourne School of Population and Global Health
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    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), https://doi.org/10.1038/s41467-020-19473-7.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/252269
    DOI
    10.1038/s41467-020-19473-7
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655942
    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.

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