Dataset Information

Characterization of Bulk Phosphatidylcholine Compositions in Human Plasma Using Side-Chain Resolving Lipidomics.

ABSTRACT: Kit-based assays, such as AbsoluteIDQ^TM p150, are widely used in large cohort studies and provide a standardized method to quantify blood concentrations of phosphatidylcholines (PCs). Many disease-relevant associations of PCs were reported using this method. However, their interpretation is hampered by lack of functionally-relevant information on the detailed fatty acid side-chain compositions as only the total number of carbon atoms and double bonds is identified by the kit. To enable more substantiated interpretations, we characterized these PC sums using the side-chain resolving Lipidyzer^TM platform, analyzing 223 samples in parallel to the AbsoluteIDQ^TM. Combining these datasets, we estimated the quantitative composition of PC sums and subsequently tested their replication in an independent cohort. We identified major constituents of 28 PC sums, revealing also various unexpected compositions. As an example, PC 16:0_22:5 accounted for more than 50% of the PC sum with in total 38 carbon atoms and 5 double bonds (PC aa 38:5). For 13 PC sums, we found relatively high abundances of odd-chain fatty acids. In conclusion, our study provides insights in PC compositions in human plasma, facilitating interpretation of existing epidemiological data sets and potentially enabling imputation of PC compositions for future meta-analyses of lipidomics data.

SUBMITTER: Quell JD

PROVIDER: S-EPMC6631474 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Characterization of Bulk Phosphatidylcholine Compositions in Human Plasma Using Side-Chain Resolving Lipidomics.

Quell Jan D JD Römisch-Margl Werner W Haid Mark M Krumsiek Jan J Skurk Thomas T Halama Anna A Stephan Nisha N Adamski Jerzy J Hauner Hans H Mook-Kanamori Dennis D Mohney Robert P RP Daniel Hannelore H Suhre Karsten K Kastenmüller Gabi G

Metabolites 20190608 6

Kit-based assays, such as Absolute<i>IDQ</i><sup>TM</sup> p150, are widely used in large cohort studies and provide a standardized method to quantify blood concentrations of phosphatidylcholines (PCs). Many disease-relevant associations of PCs were reported using this method. However, their interpretation is hampered by lack of functionally-relevant information on the detailed fatty acid side-chain compositions as only the total number of carbon atoms and double bonds is identified by the kit. T ...[more]

PMID: 31181753

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Project description:BackgroundThe development of plasma biomarkers could facilitate early detection, risk assessment and therapeutic monitoring in Alzheimer's disease (AD). Alterations in ceramides and sphingomyelins have been postulated to play a role in amyloidogensis and inflammatory stress related neuronal apoptosis; however few studies have conducted a comprehensive analysis of the sphingolipidome in AD plasma using analytical platforms with accuracy, sensitivity and reproducibility.Methods and findingsWe prospectively analyzed plasma from 26 AD patients (mean MMSE 21) and 26 cognitively normal controls in a non-targeted approach using multi-dimensional mass spectrometry-based shotgun lipidomics to determine the levels of over 800 molecular species of lipids. These data were then correlated with diagnosis, apolipoprotein E4 genotype and cognitive performance. Plasma levels of species of sphingolipids were significantly altered in AD. Of the 33 sphingomyelin species tested, 8 molecular species, particularly those containing long aliphatic chains such as 22 and 24 carbon atoms, were significantly lower (p<0.05) in AD compared to controls. Levels of 2 ceramide species (N16:0 and N21:0) were significantly higher in AD (p<0.05) with a similar, but weaker, trend for 5 other species. Ratios of ceramide to sphingomyelin species containing identical fatty acyl chains differed significantly between AD patients and controls. MMSE scores were correlated with altered mass levels of both N20:2 SM and OH-N25:0 ceramides (p<0.004) though lipid abnormalities were observed in mild and moderate AD. Within AD subjects, there were also genotype specific differences.ConclusionsIn this prospective study, we used a sensitive multimodality platform to identify and characterize an essentially uniform but opposite pattern of disruption in sphingomyelin and ceramide mass levels in AD plasma. Given the role of brain sphingolipids in neuronal function, our findings provide new insights into the AD sphingolipidome and the potential use of metabolomic signatures as peripheral biomarkers.

Dataset Information

Characterization of Bulk Phosphatidylcholine Compositions in Human Plasma Using Side-Chain Resolving Lipidomics.

Publications

Characterization of Bulk Phosphatidylcholine Compositions in Human Plasma Using Side-Chain Resolving Lipidomics.

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