期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 76, 期 1, 页码 303-315出版社
IOS PRESS
DOI: 10.3233/JAD-191304
关键词
Aging; Alzheimer's disease; APOE epsilon 4; gender; lipid species
资金
- Commonwealth Scientific Industrial and research Organization (CSIRO)
- Edith Cowan University (ECU)
- Mental Health Research institute (MHRI)
- National Ageing Research Institute (NARI)
- Austin Health
- CogState Ltd.
- National Health and Medical Research Council (NHMRC)
- Dementia Collaborative Research Centres program (DCRC2)
- Science and Industry Endowment Fund (SIEF)
- Cooperative Research Centre (CRC) for Mental Health - funded through the CRC Program [20100104]
- Australian Government Initiative
- Dementia Australia Research Foundation Scholarship
- National Health and Medical Research Council of Australia
- Victorian Government's Operational Infrastructure Support Program
Background: Lipid metabolism is altered in Alzheimer's disease (AD); however, the relationship between AD risk factors (age, APOE epsilon 4, 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, APOE epsilon 4 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 APOE epsilon 4 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.
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