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

Laura de Boni, Linda Riedel, Ina Schmitt, Theo F.J. Kraus, Oliver Kaut, Dominik Piston, Schahram Akbarian, Ullrich Wüllner

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish
Pages (from-to)3334.e7-3334.e11
JournalNeurobiology of Aging
Volume36
Issue number12
DOIs
StatePublished - Dec 2015

Keywords

  • Aging
  • Cell-specific DNA methylation
  • Neurons
  • SNCA

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