Relationships between plasma lipids species, gender, risk factors, and Alzheimer’s disease

Wei Ling Florence Lim, Kevin Huynh, Pratishtha Chatterjee, Ian Martins, Kaushala S. Jayawardana, Corey Giles, Natalie A. Mellett, Simon M. Laws, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Brian G. Drew, Colin L. Masters, Peter J. Meikle, Ralph N. Martins, The AIBL Research Group

Research output: Contribution to journalArticle

Abstract

Background: Lipid metabolism is altered in Alzheimer's disease (AD); however, the relationship between AD risk factors (age, APOEɛ4, and gender) and lipid metabolism is not well defined. Objective: We investigated whether altered lipid metabolism associated with increased age, gender, and APOE status may contribute to the development of AD by examining these risk factors in healthy controls and also clinically diagnosed AD individuals. Methods: We performed plasma lipidomic profiling (582 lipid species) of the Australian Imaging, Biomarkers and Lifestyle flagship study of aging cohort (AIBL) using liquid chromatography-mass spectrometry. Linear regression and interaction analysis were used to explore the relationship between risk factors and plasma lipid species. Results: We observed strong associations between plasma lipid species with gender and increasing age in cognitively normal individuals. However, APOEɛ4 was relatively weakly associated with plasma lipid species. Interaction analysis identified differential associations of sphingolipids and polyunsaturated fatty acid esterified lipid species with AD based on age and gender, respectively. These data indicate that the risk associated with age, gender, and APOEɛ4 may, in part, be mediated by changes in lipid metabolism. Conclusion: This study extends our existing knowledge of the relationship between the lipidome and AD and highlights the complexity of the relationships between lipid metabolism and AD at different ages and between men and women. This has important implications for how we assess AD risk and also for potential therapeutic strategies involving modulation of lipid metabolic pathways.

Original languageEnglish
Pages (from-to)303-315
Number of pages13
JournalJournal of Alzheimer's Disease
Volume76
Issue number1
DOIs
Publication statusPublished - 2020

Bibliographical note

Copyright IOS Press and 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.

Keywords

  • Aging
  • Alzheimer’s disease
  • APOE ɛ4
  • gender
  • lipid species

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    Lim, W. L. F., Huynh, K., Chatterjee, P., Martins, I., Jayawardana, K. S., Giles, C., ... The AIBL Research Group (2020). Relationships between plasma lipids species, gender, risk factors, and Alzheimer’s disease. Journal of Alzheimer's Disease, 76(1), 303-315. https://doi.org/10.3233/JAD-191304