title: Profiling brain and plasma lipids in human APOE epsilon2, epsilon3, and epsilon4 knock-in mice using electrospray ionization mass spectrometry.
abstract: 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 epsilon2, epsilon3, and epsilon4 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 epsilon2 and epsilon4 mice compared to APOE epsilon3 mice. However, overall, we did not observe any major effects in APOE epsilon4 knock-in mice for the levels of the glycerophospholipids measured, as compared to APOE epsilon2 and epsilon3 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 epsilon4 is not associated with disturbances in brain sterol or sphingolipids in the absence of environmental factors.
authors.affiliation: Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, WA, Australia.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Sharman
authors.forename: Guanghou
authors.initials: G
authors.lastname: Shui
authors.forename: Aaron Z
authors.initials: AZ
authors.lastname: Fernandis
authors.forename: Wei Ling F
authors.initials: WL
authors.lastname: Lim
authors.forename: Tamar
authors.initials: T
authors.lastname: Berger
authors.forename: Eugene
authors.initials: E
authors.lastname: Hone
authors.forename: Kevin
authors.initials: K
authors.lastname: Taddei
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Martins
authors.forename: Jorge
authors.initials: J
authors.lastname: Ghiso
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Buxbaum
authors.forename: Sam
authors.initials: S
authors.lastname: Gandy
authors.forename: Markus R
authors.initials: MR
authors.lastname: Wenk
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
mesh_terms: D000367:Age Factors; D000818:Animals; D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010949:Plasma / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods
chemical_list: D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D008055:Lipids