The University of Tokyo, Graduate School of Medicine, Lipidomics Laboratory, Hongo, Bunkyo-Ku, Tokyo.
PLoS One. 2019 Dec 10;14(12):e0226073. doi: 10.1371/journal.pone.0226073. eCollection 2019.
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.
同位素质谱标签法在蛋白质组学和脂质组学领域得到广泛应用，采用三重四极杆质谱仪的多重反应监测 (MRM) 方法，用于鉴定阿尔茨海默病（AD）患者血浆样本中的生物标志物候选物。我们重点关注具有氨基作为官能团的以下磷脂：磷脂酰乙醇胺 (PE)、溶血磷脂酰乙醇胺 (Lyso-PE)、磷脂酰丝氨酸和溶血磷脂酰丝氨酸。我们还研究了具有羧基的脂肪酸。在这项研究中，六重串联质量标签 (TMT) 用于同位素质谱标签法。TMT 反应在人血浆中具有高重现性。本研究共使用了来自三个 AD 队列的 196 个人类血浆样本，并与混合血浆质量控制 (QC) 样本进行了比较。该方法仅需要进行 40 次 MRM 测量，包括混合 QC 样本，即可对数据进行全面比较。我们发现，在所有三个队列中，AD 样本中的游离脂肪酸含量增加，AD 患者的烯基 PEs (ePEs) 在一年的时间间隔内减少，并且 ePEs 与脑脊液中的淀粉样肽 (a-beta) 1-42 弱相关。总之，血浆中总游离脂肪酸是 AD 的一个风险因素，ePEs 监测 AD 的候选物。因此，TMT-脂质组学是一种强大的血浆生物标志物测定方法，因为它具有高通量的样本处理能力。
