Glucosylceramides (GlcCers) and galactosylceramides (GalCers) are structurally related lipids that are important for mammalian cells. However, their presence in the body is tissue-specific, and problems with the body’s ability to maintain the right balance of theses lipids can lead to devastating but drastically different diseases. For example, mutations in GBA gene with deficient glucosylcerebrosidase lead to build up of GlcCer in cells and the production of toxic glucosylsphingosine. Individuals with mutations of GBA gene also present higher risk of developing Parkinson’s disease. On the other hand, people with mutations in the GALC gene develop Krabbe disease due to cell’s inability to clear GalCer and the production of toxic galactosylsphingosine. Thus, specific profiling and quantification of GlcCer and GalCer are essential for biomarker discovery and drug screening. The specific quantification of GlcCer and GalCer is, however, particularly challenging due to their virtually identical structures (Figure 1). To address this challenge, we developed a new liquid chromatography mass spectrometry (LC/MS)-based method using differential ion mobility spectrometry (DMS) to allow rapid and reproducible separation and quantification of structurally very similar GlcCer and GalCer in a single run (Figure 2). We have shown that our method is capable of quantifying specific GlcCer and GalCer in human plasma and cerebrospinal fluid (CSF). As human CSF is a scarce and precious resource, particularly from disease-specific biobanks, this method facilitates measurement in the applied neurological research setting.

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