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Targeted metabolomics reveals altered oxylipin profiles in plasma of mild cognitive impairment patients

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Abstract

Introduction and objective

Mild cognitive impairment (MCI) is considered to be a prodromal stage of Alzheimer’s disease (AD), which is the most common type of dementia. Although MCI is a common clinical manifestation in the elderly, the pathology and molecular mechanisms are not fully understood. Oxylipins are a major class of lipid-derived signaling mediators, which have been implicated in the pathology of MCI and AD. In this study, we investigated the changes of oxylipin profiles in plasma of MCI patients.

Methods

We performed a targeted liquid chromatography—mass spectrometry analysis to quantify 49 oxylipins and 4 polyunsaturated fatty acids in plasma samples of 60 clinically diagnosed MCI patients and 56 age- and gender-matched cognitively normal individuals.

Results

We found that the levels of linoleic acid (LA) and 7 oxylipins were significantly altered in MCI patients when compared to the controls. Notably, oxylipins synthesized through 5-lipoxygenase (5-LOX) and cytochrome P450 (CYP450) pathways of arachidonic acid (AA) or LA were elevated in MCI patients, which is in accordance with previously reports that oxylipins from the same pathways were increased in the brain tissues of AD and MCI patients, suggesting the potential correlations of oxylipin changes in 5-LOX and CYP450 pathways between the peripheral blood and the brain tissues in MCI and AD patients.

Conclusion

This study is the first report on plasma oxylipin profiles in MCI patients, and disease-relevant changes of oxylipins and oxylipin pathways were identified. The results represent potentially an efficient method to monitor certain oxylipin changes in the brain tissues of MCI or AD patients.

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Acknowledgements

This work is supported by the National University of Singapore Virtual Institute for the Study of Ageing [grant number VG-8]; the Alice Lim Memorial Fund, Singapore [Grant Number ALMFA/2010]; the National Medical Research Council of Singapore [Grant Number NMRC/TA/0053/2016].

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Author notes

  1. Jinling Fang and Liang Cui have contributed equally to this work.

Authors and Affiliations

  1. Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore

    Jinling Fang & Choon Nam Ong

  2. Infectious Diseases Interdisciplinary Research Group, Singapore-MIT Alliance for Research & Technology (SMART), Singapore, Singapore

    Liang Cui

  3. Department of Psychological Medicine, National University of Singapore, Singapore, Singapore

    Ye Sun & Lei Feng

  4. NUS Environment Research Institute, National University of Singapore, Singapore, Singapore

    Choon Nam Ong

Authors
  1. Jinling Fang
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  2. Liang Cui
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  3. Ye Sun
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  4. Lei Feng
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  5. Choon Nam Ong
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Corresponding authors

Correspondence to Lei Feng or Choon Nam Ong.

Electronic supplementary material

Below is the link to the electronic supplementary material.

11306_2017_1249_MOESM1_ESM.pdf

LC-MS/MS chromatogram of 48 oxylipins and 4 polyunsaturated fatty acids performed on a triple quadrupole with multiple reaction monitoring (MRM) in negative mode.Supplementary material 1 (PDF 58 KB)

11306_2017_1249_MOESM2_ESM.pdf

Receiver Operating Curve of the significantly altered oxylipins and linoleic acid in MCI patients. The sensitivity and specificity refer to distinguishing MCI patients and controls. Supplementary material 2 (PDF 5 KB)

Supplementary material 3 (DOCX 20 KB)

Supplementary material 4 (DOCX 21 KB)

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Fang, J., Cui, L., Sun, Y. et al. Targeted metabolomics reveals altered oxylipin profiles in plasma of mild cognitive impairment patients. Metabolomics 13, 112 (2017). https://doi.org/10.1007/s11306-017-1249-0

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