Profiling Brain and Plasma Lipids in Human APOE ε2, ε3, and ε4 Knock-in Mice Using Electrospray Ionization Mass Spectrometry
Authors
- Matthew Sharman, Edith Cowan University
- Guanghou Shui
- Aaron Fernandis
- Wei Ling F Lim
- Tamar Berger
- Eugene Hone
- Kevin Taddei, Edith Cowan UniversityFollow
- Ian Martins, Edith Cowan UniversityFollow
- Jorge Ghiso
- Joseph D Buxbaum
- Sam Gandy, Edith Cowan University
- Markus Wenk
- Ralph Martins, Edith Cowan University
Document Type
Journal Article
Keywords
It is known that apolipoprotein E (ApoE) is essential for normal lipid metabolism. ApoE is the major apolipoprotein in the central nervous system and plays a key role in neurobiology by mediating the transport of cholesterol, phospholipids, and sulfatides. We therefore examined APOE ε2, ε3, and ε4 knock-in mice, using electrospray ionization mass spectrometry to determine if APOE genotype or age leads to altered levels in the brain of a number of glycerophospholipids (phosphatidylinositol, PI, phosphatidylethanolamine, PE, phosphatidic acid, PA, phosphatidylserine, PS, phosphatidylcholine, PC), sphingolipids (sphingomyelin, SM, ceramide, Cer), cholesterol, and triacylglycerols. We observed slight changes within individual PI, PE, PC, Cer, and SM lipid levels in APOE ε2 and ε4 mice compared to APOE ε3 mice. However, overall, we did not observe any major effects in APOE ε4 knock-in mice for the levels of the glycerophospholipids measured, as compared to APOE ε2 and ε3 mice. Our findings indicate that variations in ApoE isoforms do not per se affect bulk lipid homeostasis in the brain. These findings indicate that APOE ε4 is not associated with disturbances in brain sterol or sphingolipids in the absence of environmental factors.
Publisher
IOS Press
Faculty
Faculty of Computing, Health and Science
School
School of Exercise, Biomedical and Health Science / Centre of Excellence for Alzheimer's Disease Research and Care
RAS ID
10478
Abstract
Alzheimer's disease, APOE genotype, cholesterol, glycerophospholipids, lipidomics, sphingolipids
Comments
Sharman, M. J., Shui, G., Fernandis, A., Lim, W., Berger, T., Hone, E., Taddei, K. , Martins, I. J., Ghiso, J., Buxbaum, J., Gandy, S. , Wenk, M., & Martins, R. N. (2010). Profiling brain and plasma lipids in human APOE ε2, ε3 and ε4 knock-in mice using electrospray ionization mass spectrometry. Journal of Alzheimer's Disease, 20(1), 105-111. Available here