Simultaneous Mass Spectrometry-Based Apolipoprotein Profiling and Apolipoprotein E Phenotyping in Patients with ASCVD and Mild Cognitive Impairment
Open accessAbstract
Apolipoprotein E (apoE) occurs on the majority of plasma lipoproteins and plays a major role in the lipid metabolism in the periphery and in the central nervous system. ApoE is a polymorphic protein with three common isoforms, apoE2, apoE3 and apoE4, derived from respective alleles ε2, ε3 and ε4. The aim of this study was to develop a sample pretreatment protocol combined with rapid mass spectrometry (MS)-based assay for simultaneous apolipoprotein profiling and apoE phenotype identification. This assay was validated in 481 samples from patients with stable atherosclerotic cardiovascular disease (ASCVD) and applied to study association with mild cognitive impairment (MCI) in the LIFE Adult study, including overall 690 study subjects. Simultaneous quantification of 8–12 major apolipoproteins including apoA-I, apoB-100 and apoE could be performed within 6.5 min. Phenotyping determined with the developed MS assay had good agreement with the genotyping by real-time fluorescence PCR (97.5%). ApoE2 isoform was associated with the highest total apoE concentration compared to apoE3 and apoE4 (p < 0.001). In the subgroup of diabetic atherosclerotic cardiovascular disease (ASCVD) patients, apoE2 isoform was related to higher apoC-I levels (apoE2 vs. apoE3, p < 0.05), while in the subgroup of ASCVD patients under statin therapy apoE2 was related to lower apoB-100 levels (apoE2 vs. apoE3/apoE4, p < 0.05). A significant difference in apoE concentration observed between mild cognitive impairment (MCI) subjects and controls was confirmed for each apoE phenotype. In conclusion, this study provides evidence for the successful implementation of an MS-based apoE phenotyping assay, which can be used to assess phenotype effects on plasma lipid and apolipoprotein levels.
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- Authors
- Begcevic Brkovic, I., Zöhrer, B., Scholz, M., Reinicke, M., Dittrich, J., Kamalsada, S., Baber, R., Beutner, F., Teren, A., Engel, C., Wirkner, K., Thiele, H., Löffler, M., Riedel-Heller, S. G., & Ceglarek, U.
- Affiliations
- Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Leipzig University, 04103 Leipzig, Germany
- Karolinska Institutet (SE)
- Leipzig University (DE)
- Klinikum Bielefeld (DE)
- Department of Internal Medicine/Cardiology, Heart Center Leipzig, University of Leipzig, 04289 Leipzig, Germany
- Corresponding author
- Ceglarek, Uta
- ORCID
- Venue
- Nutrients
- Publisher
- MDPI AG
- Published
- 2022-06-15
- Volume
- 14
- Issue
- 12
- Pages
- 2474
- ISSN
- 2072-6643 (ISSN-L)
- PMC
- PMC9230692
- OpenAlex
- W4283029578
- Cited by
- 13
- References
- 35
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 3
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nutrients (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Publikationen an der Universität Bielefeld (Universität Bielefeld) (submittedVersion, cc-by)
- Qucosa (Saxon State and University Library Dresden) (submittedVersion, cc-by)
- Funders
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) (209933838)
- Collaborative Research Center SFB1052 “Obesity Mechanisms” (209933838)
- ROLAND ERNST STIFTUNG für Gesundheitswesen Dresden (209933838)
- Foundation for Pathobiochemistry and Molecular Diagnostics of the German Society of Clinical Chemistry and Laboratory Medicine (DGKL) (209933838)
- Leipzig Research Center for Civilization Diseases (LIFE) (209933838)
- European Union (209933838)
- European Regional Development Fund (209933838)
- Free State of Saxony (209933838)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Physical Sciences › Chemistry › Spectroscopy › Mass Spectrometry Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Keywords
- apolipoprotein E, apolipoprotein E2, apolipoprotein E3, APOE ε4, atherosclerotic cardiovascular disease, mild cognitive impairment, apolipoprotein A-I, apolipoprotein B-100, apolipoprotein C-I, diabetes mellitus, statin therapy, plasma lipids, mass spectrometry assay, LIFE-Adult-Study
- MeSH terms
- Apolipoproteins E, Cardiovascular Diseases, Humans, Mass Spectrometry, Protein Isoforms, Apolipoprotein B-100, Apolipoprotein E3, Apolipoprotein E4, Apolipoprotein E2, Cognitive Dysfunction
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