Study Rationale: Developing accurate and reliable biomarkers for Parkinson’s disease (PD) is critical for detecting early changes with the hope of better understanding the mechanisms of disease and slowing down its progression. Our previous research indicates that “epigenetic clocks” that track a DNA modification called methylation show promise for predicting PD phenotypes and PD symptom progression. We propose using the samples from the Systemic Synuclein Sampling Study (S4) to identify age-related changes in DNA methylation across various tissues and to determine whether DNA methylation levels and aging rates in various tissues are associated with alpha-synuclein levels and clinical measures of PD.
Hypothesis: We hypothesize that people with PD show accelerated biologic aging that is reflected in DNA methylation of the skin, colon and sub-mandibular gland tissue at different stages of progression, and that aging will be accelerated in tissues where alpha-synuclein accumulates.
Study Design: We will measure DNA methylation in blood and tissue samples and collect metabolomic data from serum and cerebral spinal fluid from all subjects from the S4 study. With this data we will generate epigenetic clocks to assess biologic aging in different tissues from people with PD and healthy controls. We will assess how aging biomarkers relate to alpha synuclein levels in different tissues and to responses of biologic systems in PD via metabolomics.
Impact on Diagnosis/Treatment of Parkinson’s disease: The study will greatly advance our understanding of accelerated tissue aging and its relation to alpha-synuclein tissue levels in PD. Epigenetic biomarkers are a promising approach to predict PD status, elucidate (peripheral) mechanisms of PD pathology and moreover, to test for efficiency of interventions.
Next Steps for Development: By correlating DNA methylation-based biomarkers of aging in easily accessible tissues (blood) with those in the skin, colon or the submandibular gland, we aim to develop an easily accessible biomarker for PD progression studies and, ultimately to relate biologic aging in peripheral tissues with PD progression and brain tissue pathology.