ABCD-Parkinson: developing a bisulfite-sequencing assay to estimate the concentration of cell-free DNA (cfDNA) in peripheral blood as a surrogate marker of brain cell degeneration
To estimate the concentration of cell-free DNA (cfDNA) in peripheral blood as a surrogate marker of brain cell degeneration.
Main applicant: Dr. Hieab Adams
Affiliation(s): Erasmus MC, Rotterdam
Abstract: There is a need for accurate disease-progression biomarkers for Parkinson’s disease (PD). Degeneration of the substantia nigra pars compacta (SNc) is a key mechanism underlying progression of PD, but is hard to measure reliably. In this project, we will employ a novel approach to measure SNc degeneration, by focusing on small cell-free DNA fragments (cfDNA) that are released by degenerated cells in the bloodstream. These fragments contain cell-type specific methylation patterns, which make the fragments traceable to their cell-of-origin. cfDNA based methylation assays are novel to the field of PD, but have already been applied successfully in other neurological disorders. We will (a) develop a whole-genome methylation assay to quantify the concentration of SNc-derived cfDNA in peripheral blood as a surrogate marker of SNc degeneration; (b) determine SNc cfDNA concentrations in repeated plasma samples of 130 deeply phenotyped people with PD; and (c) determine whether SNc cfDNA concentrations reflect clinical PD disease duration, as a measure of disease-progression.