Profiling Brain and Plasma Lipids in Human APOE ε2,ε3,and ε4 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 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.