Objective: To determine if whole blood DNA methylation profiles could distinguish Parkinson’s disease from controls and whether any changes correlate with disease progression.

Background: Parkinson’s Disease (PD) is currently diagnosed through presentation of characteristic movement symptoms. Patients presenting with these symptoms have already undergone significant dopaminergic neuron cell loss. Earlier diagnosis, aided by molecular biomarkers specific to PD, would improve overall patient care. Epigenetics, which is modified by both environmental cues and disease pathophysiology, is emerging as an important component of neurodegenerative diseases, including PD. Alterations to the PD methylome have been reported in epigenome-wide association studies. However, no studies have thus reported either the extent to which methylation changes correlate with disease progression or the degree to which they are modified by PD medications.

Method: Whole blood was collected from PD (n = 197) and healthy age/sex matched controls (n = 199) as an ongoing effort of the Harvard Biomarkers Study. Samples included longitudinal — 2 collection times:  baseline & 2 years post (follow-up). Illumina Infinium Methylation EPIC BeadChips were used to profile the methylome.

Results: In case versus control comparisons, we identified significant differentially methylated probes (DMPs) associated with PD. Among these, CYP2E1 has been previously reported as differentially methylated in PD brain tissue, suggesting that some CNS associated findings can also be identified peripherally in blood. In addition, in longitudinal analyses, many DMPs tagged genes involved in neuronal functions and immunity. Lastly, PD medications that impact dopamine metabolism and the one carbon metabolic pathway significantly altered the methylome, which was observed as a signifiicant dampening of the differential methylation profiles of PD patients taking these medications. These results will require replication in secondary cohorts identify those methylation changes that are reproducibly associated with PD.

Conclusion: Distinct methylation patterns in PD vs. controls were identified at each time-point. Certain methylation sites showed consistent changes regardless of sampling time; others only changed at either baseline or follow-up. Levodopa and COMT-inhibitors impact DNA methylation, as drug-naïve patients showed greater site specific methylation changes

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MDS Abstracts - https://www.mdsabstracts.org/abstract/longitudinal-dna-methylation-changes-in-blood-associated-with-parkinsons-disease-progression/