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 '2, '3
and '4. 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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:87522 |
| Date | 20 October 2023 |
| Creators | Begcevic Brkovic, Ilijana, Zöhrer, Benedikt, Scholz, Markus, Reinicke, Madlen, Dittrich, Julia, Kamalsada, Surab, Baber, Ronny, Beutner, Frank, Teren, Andrej, Engel, Christoph, Wirkner, Kerstin, Thiele, Holger, Löffler, Markus, Riedel-Heller, Steffi G., Ceglarek, Uta |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 2474 |
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