Abstract
© 2020, The Author(s). 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.
Keywords
Alzheimer's disease, Concordant peripheral lipidome signatures, clinical studies, lipid metabolism, Lipids
Document Type
Journal Article
Date of Publication
2020
Volume
11
Issue
1
Publication Title
Nature Communications
Publisher
Springer Nature
School
School of Medical and Health Sciences
RAS ID
32431
Funders
https://www.nature.com/articles/s41467-020-19473-7#Ack1
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Huynh, K., Lim, W. L. F., Giles, C., Jayawardana, K. S., Salim, A., Mellett, N. A., … Meikle, P. J. (2020). Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease. Nature Communications, 11, article 5698. https://doi.org/10.1038/s41467-020-19473-7