Profiling Brain and Plasma Lipids in Human APOE ε2, ε3, and ε4 Knock-in Mice Using Electrospray Ionization Mass Spectrometry

Article type: Research Article

Authors: Sharman, Matthew J.^{a; b; c; 1} | Shui, Guanghou^{d; 1} | Fernandis, Aaron Z.^d | Lim, Wei Ling F.^{c; e} | Berger, Tamar^{c; e} | Hone, Eugene^{c; e} | Taddei, Kevin^{b; c; e} | Martins, Ian J.^{a; b; c} | Ghiso, Jorge^f | Buxbaum, Joseph D.^g | Gandy, Sam^g | Wenk, Markus R.^{d; h} | Martins, Ralph N.^{a; b; c; e; *}

Affiliations: [a] Centre of Excellence for Alzheimer's Disease Research and Care, Edith Cowan University, Joondalup, WA, Australia | [b] School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia | [c] Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Hospital, Nedlands, WA, Australia | [d] Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore | [e] School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Nedlands, WA, Australia | [f] Department of Pathology, New York University School of Medicine, New York, NY, USA | [g] Mt Sinai School of Medicine, Mount Sinai, New York, NY, USA | [h] Biological Sciences, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

Correspondence: [*] Correspondence to: Ralph N. Martins, Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA 6027, Australia. Tel.: +61 8 63045456; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

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.

Keywords: Alzheimer's disease, APOE genotype, cholesterol, glycerophospholipids, lipidomics, sphingolipids

DOI: 10.3233/JAD-2010-1348

Journal: Journal of Alzheimer's Disease, vol. 20, no. 1, pp. 105-111, 2010