Ceramides as Novel Disease Biomarkers

Ceramides are sphingolipids and integral components of the eukaryotic cell membrane. Apart from providing structural integrity, ceramides have also been shown to act as second messengers in cell signaling processes. In recent publications, ceramide modulation has been reported in pathological conditions such as cancer, diabetes, Alzheimer’s disease (AD), coronary artery disease (CAD), multiple sclerosis (MS), as well as depression. Ceramides or ceramide panel combinations have been proposed as specific disease biomarkers that could be detected in diseased tissue, synovial fluid, cerebrospinal fluid (CSF), and blood. This article reviews ceramide modulation in a selection of different diseases and the potential use of ceramides as biomarkers in diagnostics, determination of disease stage and personalized medicine. Ceramides as sphingolipids are crucial to cell membrane stability and are able to act as bioactive lipids in cell signaling pathways, including inflammation, apoptosis, cell cycle arrest, and heat shock response. Consequently, ceramides are modulated in several diseases such as cancer, multiple sclerosis, type 2 diabetes (T2D), Alzheimer’s disease, and coronary artery disease (CAD). Since ceramides are detectable in easily accessible body fluids, they have recently been proposed as promising biomarker candidates. DHCer C18:0 elevation and ceramide C18:0/C16:0 ratio are predictive of T2D 9–10 years prior to diagnosis, making this a potentially interesting biomarker in terms of disease prevention. Elevated ratios of ceramides C16:0/C24:0, C18:0/C24:0, and C24:1/C24:0 as well as C16:0, C18:0, and C24:1 are associated with an increased risk of cardiac death in patients with CAD in two independent studies. A test for these ceramides is already commercially available to American laboratories.