Abstract
The isobaric tagging method widely used in proteomic and lipidomic fields, with the multiple reaction monitoring (MRM) approach using a triple quadrupole mass spectrometer, was applied to identify biomarker candidates from plasma samples for Alzheimer’s disease (AD). We focused on the following phospholipids that have amino groups as the functional group: phosphatidylethanolamine (PE), Lyso-PE, phosphatidylserine, and Lyso-phosphatidylserine. We also investigated fatty acids that have a carboxy group. A sixplex tandem mass tag (TMT) was used for the isobaric tagging method in this study. The TMT reaction had high reproducibility in human plasma. A total of 196 human plasma samples from three AD cohorts were used for the study, and compared to pooled plasma quality control (QC) samples. The described method required only 40 MRM measurements, including the pooled QC samples, for a full comparison of the data. We found that the content of free fatty acids increased in AD samples in all the three cohorts, alkenyl PEs (ePEs) decreased over a one-year interval in AD patients, and ePEs weakly correlated with amyloid peptide (a-beta) 1–42 in cerebrospinal fluid. In conclusion, total free fatty acids in plasma are a risk factor for AD, and ePEs monitor candidates for AD. Therefore, TMT-lipidomics is a powerful approach for the determination of plasma biomarkers because of the high sample throughput.
Highlights
Plasma samples are widely used in clinical diagnosis because these samples are relatively easy and less invasive to collect from patients and healthy subjects
Several studies have already established and reported the usefulness of isobaric mass tagging methods for lipids [5,6,7,8,9]. Because this is the first application to human plasma, the CV values Number of fatty acids
It has been reported that unsaturated fatty acids decrease in Alzheimer’s disease (AD) brains [20]; our results indicate that the amount of free fatty acids in peripheral blood increases, a result opposite to that observed in the brain
Summary
Plasma samples are widely used in clinical diagnosis because these samples are relatively easy and less invasive to collect from patients and healthy subjects. The amine groups of the amino acids were present in large amounts (total 0.1–1 mM in human plasma), compared with the activated carboxy groups, and they reacted prior to the TMT reagents.
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