Transcriptional and epigenetic phenomena in peripheral blood cells of monozygotic twins discordant for alzheimer's disease, a case report

J Neurol Sci. 2017 Jan 15:372:211-216. doi: 10.1016/j.jns.2016.11.052. Epub 2016 Nov 24.

Abstract

Target genes in Alzheimer's disease (AD) have been identified. In monozygotic twins discordant for AD we analysed the expression of selected genes, and their possible regulation by epigenetic mechanisms in peripheral blood mononuclear cells, possibly useful to discover biomarkers. Amyloid precursor protein, sirtuin 1 and peptidyl prolyl isomerase 1 gene expressions were highly up-regulated in the AD twin versus the healthy one. Consistently with sirtuin 1 role in controlling acetylation status, we observed a substantial reduction of the acetylation on histone 3 lysine 9, associated with gene transcription in the AD twin. Noteworthy in the AD twin we also observed an increased gene expression in two histone deacetylases (HDACs) isoforms: HDAC2 and HDAC9. A general DNA hypomethylation of all gene promoters studied was also observed in both twins. Our results unravel transcriptional and epigenetic differences potentially helpful to better understand environmental factors and phenotypic differences in monozygotic twins.

Keywords: Alzheimer’s disease; Epigenetic mechanisms; Gene expression; Monozygotic twins; Peripheral blood mononuclear cells.

Publication types

  • Case Reports
  • Twin Study

MeSH terms

  • Aged
  • Alzheimer Disease / blood
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / genetics*
  • Biomarkers / blood
  • DNA Methylation
  • Diseases in Twins / blood
  • Diseases in Twins / diagnostic imaging
  • Diseases in Twins / genetics*
  • Epigenesis, Genetic*
  • Female
  • Humans
  • Leukocytes, Mononuclear
  • Transcription, Genetic*
  • Twins, Monozygotic / genetics*

Substances

  • Biomarkers