Brain-derived cell-free DNA

Following cell death,DNA can be released into the blood plasma and other body fluids in the form of cell-free DNA(cfDNA).These DNA fragments are typically~167 bp in length,corresponding to the length of DNA wrapped around one nucleosome core(147 bp),plus DNA tails that survive endogenous DNase digestion(~10 bp).CfDNA is derived from a variety of sources,each having unique diagnostic applications.During pregnancy,fetal-derived cfDNA within an expectant mother’s blood plasma can diagnose fetal genetic abnormalities and is a well-established method for non-invasive prenatal testing.Cancer-derived cfDNA is also detectable within blood plasma by high sensitivity methods(e.g.,NGS,ddPCR)and can accurately diagnose cancers by a minimally invasive blood test(Diehl et al.,2008).The short half-life of cfDNA(<2 hours)also facilitates real-time measurement of disease burden,such as monitoring cancer relapse.There is now growing evidence of brain-derived cfDNA(bd-cfDNA)within the cerebrospinal fluid(CSF)and blood plasma.In this perspective,we review the present understanding,current challenges,and potential utility of bd-cfDNA.