Profiling brain and plasma lipids in human APOE epsilon2, epsilon3, and epsilon4 knock-in mice using electrospray ionization mass spectrometry.
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.
Sharman
Matthew J
MJ
Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, WA, Australia.
Shui
Guanghou
G
Fernandis
Aaron Z
AZ
Lim
Wei Ling F
WL
Berger
Tamar
T
Hone
Eugene
E
Taddei
Kevin
K
Martins
Ian J
IJ
Ghiso
Jorge
J
Buxbaum
Joseph D
JD
Gandy
Sam
S
Wenk
Markus R
MR
Martins
Ralph N
RN
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
D053329:Apolipoprotein E2; D053318:Apolipoprotein E3; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D008055:Lipids