Cell-free DNA methylation as a potential biomarker in brain disorders

摘要

The diagnosis of many brain disorders is challenging due to the nonspecific clinical presentation and/or the lack of accurate biomarkers. In addition, many neurological disorders show slow progression with a long asymptomatic period followed by a stage with mild clinical symptoms. This limits the potential for early detection with effective therapeutic treatment only occurring late in the course of the disease. Clearly, developing noninvasive and accurate diagnostic tools for detecting brain disorders is an unmet medical need. Altered methylation patterns in circulating cell-free DNA (cfDNA) have been implicated as useful tools for noninvasive cancer detection, prenatal diagnostics and organ transplantation assessment. Given the critical roles of DNA methylation in many brain disorders, unusual DNA methylation alternations in cfDNA could be a promising biomarker for disease diagnosis. This commentary presents an overview of investigational applications of cfDNA methylation signatures as potential molecular markers to diagnose various brain disorders. The authors' views on the technologies for cfDNA methylation analysis based on next-generation sequencing are also discussed.