Profiling of Cerebrospinal Fluid Lipids and Their Relationship with Plasma Lipids in Healthy Humans

Abstract

Lipidomics provides an overview of lipid profiles in biological systems. Although blood is commonly used for lipid profiling, cerebrospinal fluid (CSF) is more suitable for exploring lipid homeostasis in brain diseases. However, whether an individual's background affects the CSF lipid profile remains unclear, and the association between CSF and plasma lipid profiles in heathy individuals has not yet been defined. Herein, lipidomics approaches were employed to analyze CSF and plasma samples obtained from 114 healthy Japanese subjects. Results showed that the global lipid profiles differed significantly between CSF and plasma, with only 13 of 114 lipids found to be significantly correlated between the two matrices. Additionally, the CSF total protein content was the primary factor associated with CSF lipids. In the CSF, the levels of major lipids, namely, phosphatidylcholines, sphingomyelins, and cholesterolesters, correlated with CSF total protein levels. These findings indicate that CSF lipidomics can be applied to explore changes in lipid homeostasis in patients with brain diseases.

Keywords: cerebrospinal fluid; lipid profiling; lipidomics; mass spectrometry; plasma lipid.

Figure 1

Cerebrospinal fluid (CSF) and plasma lipid profiles in healthy human subjects. (a) Diagram of the ratio of each lipid class calculated using the number of individual lipids within the class in phosphoglycerolipids, sphingolipids, and neutral lipids. (b) Estimated total concentration of phosphatidylcholine (PC), ether-type PCs (PCe), phosphatidylethanolamine (PE), and ether-type PEs (PEe) in CSF and plasma. (c) Diagram of the molar ratio of PCs calculated using the estimated concentrations of individual PCs within the total PC concentrations. (d) Fatty acid levels within PCs. Abundance of each fatty acid as percentage of all side chains, calculated as the ratio of the sum of concentrations containing the fatty acid to 2× the sum of peak heights of all PCs. (e) Compositions of ether-type and plasmalogen-type within PCes and PEes. The molar ratios of ether-type and plasmalogen-type were calculated using the estimated sum concentrations of ether-type and plasmalogen-type within the total PCe or PEe concentrations. Data are shown mean ± standard deviation.

Figure 2

Cerebrospinal fluid (CSF)–plasma correlations of lipids in healthy human subjects. (a) Individual lipid plot of false discovery rate (FDR) and correlation coefficients (r) in all subjects. (b) Individual plot of representative lipids correlated among CSF and plasma. (c) Individual lipid plot of FDR and correlation coefficients in ≤40 (younger group) and >40 (older group) years-old subjects. (d) Venn diagram of correlated lipids in all, younger, and older subjects. (e) Individual plot of age-specific representative lipids correlated among CSF and plasma. (f) Individual lipid plot of FDR and r in female and male subjects. (g) Venn diagram of correlated lipids in all, female, and male subjects. (h) Individual plot of sex-specific representative lipids correlated among CSF and plasma.

Figure 3

Effects of cerebrospinal fluid (CSF) properties on CSF lipids. (a) Individual lipid plot of false discovery rate (FDR) and estimated beta corresponding to 10 mg/mL of CSF total protein levels. (b) Individual lipid plot of correlation coefficients to CSF total protein levels. (c) Extracted individual lipid plot of FDR and correlation coefficients of phosphatidylethanolamine (PEs) and ether-type PEs (PEes).

Figure 4

Effects of age and sex on cerebrospinal fluid (CSF) lipids. (a) Individual lipid plot of false discovery rate (FDR) and estimated beta corresponding to 20 years of age and sex. (b) Individual plot of representative lipids correlated with age. (c) Individual plot of representative lipids differing between males and females.

Figure 5

Effects of the background of the subjects on cerebrospinal fluid (CSF) lipids. (a) Individual lipid plot of false discovery rate (FDR) and effect size or correlation coefficients. (b) Individual plot of representative lipids altered by allergy and alcohol habits.