Elevated Plasma Ceramides Are Associated With Higher White Matter Hyperintensity Volume-Brief Report

Area of Science:

• Neuroscience
• Cardiovascular Science
• Metabolomics

Background:

• Sphingolipids, including ceramides and sphingosine-1-phosphate (S1P), are implicated in cardiovascular regulation.
• The association between plasma sphingolipids and cerebrovascular disease, particularly white matter hyperintensity (WMH) volume, remains underexplored.

Purpose of the Study:

• To investigate the cross-sectional relationship between plasma sphingolipid levels and WMH volume in an aging population.
• To determine if specific ceramides or S1P are associated with markers of cerebrovascular disease.

Main Methods:

• Analysis of plasma sphingolipids (ceramides and S1P) using liquid chromatography-electrospray ionization tandem mass spectrometry.
• Measurement of white matter hyperintensity (WMH) volume via MRI in 588 participants from the Mayo Clinic Study of Aging.
• Linear regression models were used to assess associations, adjusting for age, sex, and hypertension.

Main Results:

• Higher plasma levels of ceramide C16:0 and specific ceramide ratios (C16:0_24:0 and C24:1_24:0) were significantly associated with increased WMH volume.
• A composite ceramide score also showed a positive association with WMH volume.
• No significant association was found between plasma S1P levels and WMH volume.

Conclusions:

• Specific plasma ceramides and their ratios are independently associated with greater white matter hyperintensity (WMH) volume.
• These findings suggest that plasma ceramides may be valuable biomarkers for assessing cerebrovascular disease burden.