Analytical and Bioanalytical Chemistry

, Volume 410, Issue 12, pp 2937–2948 | Cite as

Characterization of potential plasma biomarkers related to cognitive impairment by untargeted profiling of phospholipids using the HILIC-ESI-IT-TOF-MS system

  • Shuang Song
  • Ling-Zhi Cheong
  • Qing-Qing Man
  • Shao-Jie Pang
  • Yue-Qi Li
  • Biao Ren
  • Jian Zhang
Research Paper


Early diagnosis of neural changes causing cognitive impairment is critical for development of preventive therapies for dementia. Biomarkers currently characterized cannot be extensively applied due to the invasive sampling of cerebrospinal fluid. The other imaging approaches are either expensive or require a high technique. Phospholipids (PLs), which are basic constituents of neurons, might be a key variable in the pathogenesis of cognitive impairment. Changes in plasma PL provide the possibility for development of novel biomarkers with minimal invasion and high patient acceptance. In this work, a HILIC-ESI-IT-TOF-MS system was introduced for untargeted profiling of plasma PLs to investigate the relationship between changes of plasma PL profiles and cognitive impairment. A total of 272 types of PL molecular structures were characterized in human plasma and quantified through the internal standard method. Univariate analysis shows 29 PLs were significantly different between the control (n = 41) and the cognitive impairment (CI) group (n = 41). Multivariate analysis (PCA and OPLS-DA) was conducted based on these 29 potential PL biomarkers. Both univariate and multivariate analyses show abnormality of PL metabolism in the CI group, and the downregulation of ethanolamine plasmalogen (pPE) supply, especially those with PUFAs, in the circulation system should be strongly associated with neurodegeneration. A discriminative model was established with satisfied fit (R2) and prediction (Q2) abilities, and the classification test showed better recognition of the CI group than the control group indicating that this model of PL biomarkers could be used as indicators for screening of CI.

Graphical abstract

Characterization of potential plasma biomarkers related to cognitive impairment by untargeted profiling of phospholipids


Phospholipid LC-MS Biomarker Cognitive impairment 



We specially acknowledge the help of Shimadzu (China) with the MS technical support.

Funding information

This work was supported by the Natural Science Foundation of China (81372991) and the youth fund of National Institute for Nutrition and Health (NINH2016002).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Involvement of human participants and informed consent

Human participants were volunteers from two communities. Human blood samples were collected from volunteers in this study. This work was performed with the informed consent signed by all the volunteers. The study was approved by The Ethics Committee of National Institute for Nutrition and Health and performed in accordance of the ethical standards.

Supplementary material

216_2018_975_MOESM1_ESM.pdf (878 kb)
ESM 1 (PDF 878 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Shuang Song
    • 1
  • Ling-Zhi Cheong
    • 2
  • Qing-Qing Man
    • 1
  • Shao-Jie Pang
    • 1
  • Yue-Qi Li
    • 3
  • Biao Ren
    • 3
  • Jian Zhang
    • 1
  1. 1.National Institute for Nutrition and HealthChinese Center for Disease Control and PreventionBeijingChina
  2. 2.Department of Food Science, School of Marine ScienceNingbo UniversityNingboChina
  3. 3.Beijing Analysis CenterShimadzu International Trade (China) Co.BeijingChina

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