title: DNA methylation levels of α-synuclein intron 1 in the aging brain.
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.
authors.affiliation: Department of Neurology, University Clinic, University of Bonn, Bonn, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: de Boni
authors.affiliation: Department of Neurology, University Clinic, University of Bonn, Bonn, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Riedel
authors.affiliation: Department of Neurology, German Center for Neurodegenerative Diseases (DZNE), University of Bonn, Bonn, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Schmitt
authors.affiliation: Center for Neuropathology and Prion Research (ZNP), Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Theo F J
authors.initials: TFJ
authors.lastname: Kraus
authors.affiliation: Department of Neurology, University Clinic, University of Bonn, Bonn, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kaut
authors.affiliation: Department of Neurology, German Center for Neurodegenerative Diseases (DZNE), University of Bonn, Bonn, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Piston
authors.affiliation: Icahn School of Medicine at Mount Sinai, Hess Center for Science and Medicine, New York, NY, USA.
authors.forename: Schahram
authors.initials: S
authors.lastname: Akbarian
authors.affiliation: Department 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.
authors.forename: Ullrich
authors.initials: U
authors.lastname: Wüllner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D001921:Brain / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007438:Introns / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics; D012307:Risk Factors; D055815:Young Adult; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
chemical_list: C497604:SNCA protein, human; D051844:alpha-Synuclein
keywords: Aging; Cell-specific DNA methylation; Neurons; SNCA