Global changes in DNA methylation in Alzheimer's disease peripheral blood mononuclear cells

Andrea Di Francesco, Beatrice Arosio, Anastasia Falconi, Maria Vittoria Micioni Di Bonaventura, Mohsen Karimi, Daniela Mari, Martina Casati, Mauro Maccarrone, Claudio D'Addario

Research output: Contribution to journalArticle

Abstract

Changes in epigenetic marks may help explain the late onset of Alzheimer's disease (AD). In this study we measured genome-wide DNA methylation by luminometric methylation assay, a quantitative measurement of genome-wide DNA methylation, on DNA isolated from peripheral blood mononuclear cells of 37 subjects with late-onset AD (LOAD) and 44 healthy controls (CT). We found an increase in global DNA methylation in LOAD subjects compared to CT (p= 0.0122), associated with worse cognitive performances (p= 0.0002). DNA hypermethylation in LOAD group was paralleled by higher DNA methyltransferase 1 (DNMT1) gene expression and protein levels. When data were stratified on the basis of the APOE polymorphisms, higher DNA methylation levels were associated with the presence of APOE ε4 allele (p= 0.0043) in the global population. Among the APOE ε3 carriers, a significant increase of DNA methylation was still observed in LOAD patients compared to healthy controls (p= 0.05). Our data suggest global DNA methylation in peripheral samples as a useful marker for screening individuals at risk of developing AD.

Original languageEnglish
Pages (from-to)139-144
Number of pages6
JournalBrain, Behavior, and Immunity
Volume45
DOIs
Publication statusPublished - Mar 1 2015

Keywords

  • Alzheimer's disease
  • APOE
  • DNA methylation
  • DNMT
  • Epigenetics
  • PBMC
  • Peripheral markers
  • Pyrosequencing

ASJC Scopus subject areas

  • Immunology
  • Behavioral Neuroscience
  • Endocrine and Autonomic Systems
  • Medicine(all)

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  • Cite this

    Di Francesco, A., Arosio, B., Falconi, A., Micioni Di Bonaventura, M. V., Karimi, M., Mari, D., Casati, M., Maccarrone, M., & D'Addario, C. (2015). Global changes in DNA methylation in Alzheimer's disease peripheral blood mononuclear cells. Brain, Behavior, and Immunity, 45, 139-144. https://doi.org/10.1016/j.bbi.2014.11.002