Abstract
Parkinson disease (PD) is a multifactorial neurodegenerative disorder with high incidence in the elderly, where environmental and genetic factors are involved in etiology. In addition, epigenetic mechanisms, including deregulation of DNA methylation have been recently associated to PD. As accurate diagnosis cannot be achieved pre-mortem, identification of early pathological changes is crucial to enable therapeutic interventions before major neuropathological damage occurs. Here we investigated genome-wide DNA methylation in brain and blood samples from PD patients and observed a distinctive pattern of methylation involving many genes previously associated to PD, therefore supporting the role of epigenetic alterations as a molecular mechanism in neurodegeneration. Importantly, we identified concordant methylation alterations in brain and blood, suggesting that blood might hold promise as a surrogate for brain tissue to detect DNA methylation in PD and as a source for biomarker discovery.
Submitted
06/04/13
Revised
07/17/13
Accepted
07/23/13
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
We thank Dr Robin Guariglia, Dr Randy Woltjer and Dr Joseph Quinn at the Layton Aging and Alzheimer Research Center from OHSU, supported by NIH grant NIA-AG08017 and Dr Edward Koo and Mr. Floyd Sarzosa at the Shiley-Marcos Alzheimer Disease Research Center from UCSD, supported by NIH grant AG051331, for contributing the tissues analyzed in this study. We want to thank specially to donors and their families for their invaluable contribution. We also thank Dr Nicholas Beckloff and Dr Simone Edelheit at the CWRU Department of Genetics and Genome Sciences Genomics Core Laboratory from Case Western Reserve University for DNA processing and microarray hybridization. We also thank statistician James Proudfoot from UCSD Clinical Translational Research Institute for assistance with bootstrap analysis. This work was supported by NIH grants AG5131 and AG18440 to EM.
Author Contributions
EM contributed to study design, advised on neuropathological selection of cases included and contributed to write the paper. WD performed microarray validation experiments by qPCR. DG analyzed the clinical data and contributed to the discussion. PD designed and supervised the study; obtained DNA from postmortem samples, analyzed the data and wrote the paper.
Supplemental Materials
Supplemental materials may be found here: http://www.landesbioscience.com/journals/epigenetics/article/25865