Comprehensive Methylation Profile of CSF cf DNA Revealed Pathogenesis and Diagnostic Markers for Early-Onset Parkinson’s Disease

Background: Early-onset Parkinson's disease (EOPD) is one uncommon Parkinson's disease subtype with characteristic clinicopathological features. The full epigenomic profile of EOPD is largely unknown. Methods: We performed the first study to investigate the EOPD full methylation profile of cerebrospinal fluid (CSF) cell-free DNA (cfDNA) from 26 EOPD patients and 10 control patients. Results: 2220 differentially methylated genes were identified in EOPD. Hypermethylation far outweighed hypomethylation in gene numbers. Clustering and enrichment analyses identified aberrant neuronal function and immune response. Weighted correlation network analysis demonstrated significant correlation between methylation signatures and clock drawing test (CDT), mini-mental state examination (MMSE), education, working status, alcohol drinking history and Hamilton anxiety scale (HAMA). Several key networking genes in EOPD aberrant methylation were also identified. Conclusions: The methylation profile and signatures of CSF cfDNA were revealed for the first time in EOPD. Aberrant methylation signatures were correlated with education, working status, alcohol drinking history, CDT, MMSE and HAMA.