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Neurobiol Aging. 2015 Dec;36(12):3334.e7-11. doi: 10.1016/j.neurobiolaging.2015.08.028. Epub 2015 Sep 8.

DNA methylation levels of α-synuclein intron 1 in the aging brain.

Author information

  • 1Department of Neurology, University Clinic, University of Bonn, Bonn, Germany.
  • 2Department of Neurology, German Center for Neurodegenerative Diseases (DZNE), University of Bonn, Bonn, Germany.
  • 3Center for Neuropathology and Prion Research (ZNP), Ludwig-Maximilians-University of Munich, Munich, Germany.
  • 4Icahn School of Medicine at Mount Sinai, Hess Center for Science and Medicine, New York, NY, USA.
  • 5Department of Neurology, University Clinic, University of Bonn, Bonn, Germany; Department of Neurology, German Center for Neurodegenerative Diseases (DZNE), University of Bonn, Bonn, Germany. Electronic address: ullrich.wuellner@ukb.uni-bonn.de.

Abstract

DNA methylation patterns change with age, and aging itself is a major confounding risk factor for Parkinson's disease (PD). Duplication and triplication, that is, increased expression of the α-synuclein (SNCA) gene, cause familial PD, and demethylation of SNCA intron 1 has been shown to result in increased expression of SNCA. We thus hypothesized that age-related alterations of SNCA methylation might underly the increased susceptibility toward PD in later life. The present study sought to determine (1) whether alterations of SNCA intron 1 methylation occurred during aging, (2) whether the methylation pattern differed between men and women, and (3) whether purified neurons compared with non-neuronal cells exhibited different methylation patterns. The analysis of DNA from brain tissue and fluorescence activated cell sorting-sorted purified neurons of 41 individuals revealed only a minor increase of SNCA intron 1 DNA methylation levels in presumably healthy individuals during aging but no significant difference between men and women. Interestingly enough, methylation of SNCA intron 1 was higher in neurons compared with non-neuronal cells, although non-neuronal cells express lower levels of SNCA. Therefore, the normal pattern of SNCA methylation during aging should not result in increased expression of α-synuclein protein. It is thus likely that additional, yet not identified, mechanisms contribute to the tissue specificity of SNCA expression and the presumed dysregulation in PD.

KEYWORDS:

Aging; Cell-specific DNA methylation; Neurons; SNCA

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