Plasma sphingolipid abnormalities in neurodegenerative diseases

Hideki Oizumi; Yoko Sugimura; Tomoko Totsune; Iori Kawasaki; Saki Ohshiro; Toru Baba; Teiko Kimpara; Hiroaki Sakuma; Takafumi Hasegawa; Ichiro Kawahata; Kohji Fukunaga; Atsushi Takeda

doi:10.1371/journal.pone.0279315

Plasma sphingolipid abnormalities in neurodegenerative diseases

PLoS One. 2022 Dec 16;17(12):e0279315. doi: 10.1371/journal.pone.0279315. eCollection 2022.

Authors

Affiliations

¹ Department of Neurology, National Hospital Organization Sendai Nishitaga Hospital, Sendai, Japan.
² Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
³ Department of Pharmacology, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan.
⁴ Department of Cognitive and Motor Aging, Tohoku University Graduate School of Medicine, Sendai, Japan.

Abstract

Background: In recent years, there has been increasing evidence that several lipid metabolism abnormalities play an important role in the pathogenesis of neurodegenerative diseases. However, it is still unclear which lipid metabolism abnormalities play the most important role in neurodegenerative diseases. Plasma lipid metabolomics (lipidomics) has been shown to be an unbiased method that can be used to explore lipid metabolism abnormalities in neurodegenerative diseases. Plasma lipidomics in neurodegenerative diseases has been performed only in idiopathic Parkinson's disease (IPD) and Alzheimer's disease (AD), and comprehensive studies are needed to clarify the pathogenesis.

Methods: In this study, we investigated plasma lipids using lipidomics in individuals with neurodegenerative diseases and healthy controls (CNs). Plasma lipidomics was evaluated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in those with IPD, dementia with Lewy bodies (DLB), multiple system atrophy (MSA), AD, and progressive supranuclear palsy (PSP) and CNs.

Results: The results showed that (1) plasma sphingosine-1-phosphate (S1P) was significantly lower in all neurodegenerative disease groups (IPD, DLB, MSA, AD, and PSP) than in the CN group. (2) Plasma monohexylceramide (MonCer) and lactosylceramide (LacCer) were significantly higher in all neurodegenerative disease groups (IPD, DLB, MSA, AD, and PSP) than in the CN group. (3) Plasma MonCer levels were significantly positively correlated with plasma LacCer levels in all enrolled groups.

Conclusion: S1P, Glucosylceramide (GlcCer), the main component of MonCer, and LacCer are sphingolipids that are biosynthesized from ceramide. Recent studies have suggested that elevated GlcCer and decreased S1P levels in neurons are related to neuronal cell death and that elevated LacCer levels induce neurodegeneration by neuroinflammation. In the present study, we found decreased plasma S1P levels and elevated plasma MonCer and LacCer levels in those with neurodegenerative diseases, which is a new finding indicating the importance of abnormal sphingolipid metabolism in neurodegeneration.

Copyright: © 2022 Oizumi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / metabolism
Chromatography, Liquid
Humans
Multiple System Atrophy*
Parkinson Disease* / metabolism
Sphingolipids
Supranuclear Palsy, Progressive*
Tandem Mass Spectrometry

Substances

Sphingolipids
sphingosine 1-phosphate

Grants and funding

The funding for this study was provided by grants-in-aid for Scientific Research from the Project of Translational and Clinical Research Core Centers from the Japan Agency for Medical Research and Development (AMED) (JP17dm0107071 and JP18dm0107071 to KF and AT). This work was supported by grants-in-aid from the Research Committee of CNS Degenerative Diseases, Research on Policy Planning and Evaluation for Rare and Intractable Diseases, Health, Labor and Welfare Sciences Research Grants, the Ministry of Health, Labor and Welfare, Japan.