DNA Methylation as a Biomarker for Parkinsonís Disease
Rapid Response Innovation Awards, 2013
Objective/Rationale: † † † † † ††
We will test the hypothesis that whole blood DNA methylation in Parkinsonís disease (PD) will be altered at specific sites compared to either healthy controls or to Alzheimerís disease (AD). Specific DNA methylation changes have even been reported in peripheral tissues, such as blood in AD patients, raising the possibility that DNA methylation patterns could not only provide insights into the molecular mechanisms driving AD and PD, but also could serve as biomarkers to aid in the diagnosis and tracking of these disorders.
Project Description: † † † † † ††
In this proposal, we will profile a very well characterized set of patient DNA samples, consisting of an age and gender matched series of 26 neuropathologically confirmed† PD, 51 AD, and 31 controls. Key to this biomarker discovery effort is that the samples were drawn from clinically diagnosed patients while they were still alive and the clinical diagnosis was later confirmed neuropathologically. This sample set, therefore, maximizes diagnostic accuracy while eliminating the possibility of any post-mortem or agonal artifacts. We will determine significant methylation differences between all groups on a genome-wide level.
Relevance to Diagnosis/Treatment of Parkinsonís Disease: † † † † † † † † † ††
Molecular biomarkers for PD have proven elusive, despite extensive efforts to find them. Development of a molecular biomarker that aids in diagnosis of individuals at earlier stages of PD or of individuals at increased risk for developing PD would greatly aid in the treatment of this disease since patients could be identified and enrolled in treatment trials with the potential to prevent further dopaminergic neuron loss, and more importantly, prevent further progression of disability and perhaps even prevent progression to dementia.
We will generate data for more than 450,000 methylation sites for all patients profiled. This data will then be used to determine if altered DNA methylation may be leveraged as a biomarker to aid in the earlier diagnosis or tracking of PD and will lay the groundwork for future prospective studies in patients who may be at earlier stages of disease.
DNA methylation is a mechanism that cells use to turn certain genes on and off. Both environment and disease can affect DNA methylation. Using fully characterized sets of blood samples from people with Parkinson's disease (PD), Alzheimer's disease (AD) and from healthy people, we identified less then 20 DNA methylation changes that could distinguish people with PD from those with AD or no disease. These findings now need to be confirmed in a larger set of samples and then potentially extended to earlier stages of disease to determine if these changes in the blood, a relatively easily sampled biofluid, can be used to diagnose PD early, track its progression or monitor treatment effectiveness in clinical trials.
Presentations & Publications
Driver-Dunckley E, Meechoovet B, Caselli R, Adler C, Beach T, Dunckley T. DNA methylation as an epigenetic biomarker for Alzheimer's and Parkinson's diseases. Presented at: International Conference on Alzheimer's and Parkinson's Diseases; March 18 - 22, 2015; Nice, France.
Assistant Professor at Translational Genomics Research Institute
Location: Phoenix, Arizona, United States