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 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.
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Our findings confirm the elevated lipid levels previously observed in humanized APOE2 mice compared to those carrying APOE3 and APOE4.
“Our findings confirm the elevated lipid levels previously observed in humanized APOE2 mice compared to those carrying APOE3 and APOE4 [85].”
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Martins, R. N., Villemagne, V., Sohrabi, H. R., Chatterjee, P., Shah, T. M., Verdile, G., Fraser, P., Taddei, K., Gupta, V. B., Rainey-Smith, S. R., et al. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-171145 · Cited by 129 · see citing works
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“While our findings corroborate previous observations reporting that differential APOE isoform expression does not profoundly alter lipid composition in the brain [26, 27], significant effects were observed in the levels of less abundant and bioactive lipid species in both brain regions.”
ResultYesiltepe, M., Yin, T., Tambini, M., Bao, H., Pan, M., d’Abramo, C., Giliberto, L., Han, X., & D’Adamio, L. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01832-2 · Cited by 10 · see citing works
“Our findings confirm the elevated lipid levels previously observed in humanized APOE2 mice compared to those carrying APOE3 and APOE4 [85].”
Richards, S. E. V., Yang, M., Deik, A. A., & Ricq, E. L. (2025) · Neurochemical Research · doi:10.1007/s11064-025-04463-2 · Cited by 3 · see citing works
- Authors
- Sharman, M. J., Shui, G., Fernandis, A. Z., Lim, W. L. F., Berger, T., Hone, E., Taddei, K., Martins, I. J., Ghiso, J., Buxbaum, J. D., Gandy, S., Wenk, M. R., & Martins, R. N.
- Affiliations
- Edith Cowan University (AU)
- National University of Singapore (SG)
- The University of Western Australia (AU)
- New York University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Martins, Ralph N.
- ORCID
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2010-03-24
- Volume
- 20
- Issue
- 1
- Pages
- 105-111
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1730584303
- Cited by
- 35
- References
- 47
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 2 · 2016: 1 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 1
- FWCI
- 1.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- eCite Digital Repository (University of Tasmania) (submittedVersion)
- UWA Profiles and Research Repository (University of Western Australia) (submittedVersion)
- Edith Cowan University Research Online (Edith Cowan University) (submittedVersion)
- National University of Singapore (submittedVersion)
- Figshare (submittedVersion)
- Funders
- National Institute on Aging (P01AG010491, AG10491)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- apolipoprotein E, APOE ε2
- MeSH terms
- Age Factors, Animals, Apolipoproteins E, Brain, Humans, Lipids, Male, Mice, Transgenic, Plasma, Spectrometry, Mass, Electrospray Ionization, Mice, Apolipoprotein E3, Apolipoprotein E4, Apolipoprotein E2
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