Methylation analysis of multiple genes in blood DNA of Alzheimer's disease and healthy individuals

Neurosci Lett. 2015 Jul 23:600:143-7. doi: 10.1016/j.neulet.2015.06.009. Epub 2015 Jun 12.

Abstract

We collected blood DNA from 120 late-onset Alzheimer's disease (AD) patients and 115 healthy matched controls and analysed the methylation levels of genes involved in amyloid-beta peptide production (PSEN1 and BACE1), in DNA methylation (DNMT1, DNMT3A and DNMT3B), and in one-carbon metabolism (MTHFR), searching for correlation with age and gender, with biomarkers of one-carbon metabolism (plasma homocysteine, and serum folate and vitamin B12 levels), and with disease status (being healthy or having AD). We also evaluated the contribution of the APOE ϵ4 allele, the major late-onset AD genetic risk factor, to the studied gene methylation levels. All the genes showed low mean methylation levels (<5%) in both AD and control DNA, no difference between groups, and no correlation with the studied biomarkers, except for MTHFR that showed methylation levels ranging from 5% to 75%, and correlation with circulating biomarkers of one-carbon metabolism. However, mean MTHFR methylation levels were similar between groups (31.1% in AD and 30.7% in controls, P=0.58). Overall, present data suggest that none of the studied regions is differently methylated in blood DNA between AD and control subjects.

Keywords: APOE; Alzheimer’s disease; BACE1; DNA methylation; DNMTs; Folate; Homocysteine; MTHFR; PSEN1; Vitamin B12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Amyloid Precursor Protein Secretases / blood
  • Amyloid Precursor Protein Secretases / genetics
  • Apolipoprotein E4 / blood
  • Apolipoprotein E4 / genetics
  • Aspartic Acid Endopeptidases / blood
  • Aspartic Acid Endopeptidases / genetics
  • Biomarkers / blood
  • Case-Control Studies
  • CpG Islands
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases / blood
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA / blood*
  • DNA Methylation*
  • DNA Methyltransferase 3A
  • DNA Methyltransferase 3B
  • Female
  • Folic Acid / blood
  • Homocysteine / blood
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / blood
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Presenilin-1 / blood
  • Presenilin-1 / genetics
  • Promoter Regions, Genetic
  • Sex Factors
  • Vitamin B 12 / blood

Substances

  • 5' Untranslated Regions
  • Apolipoprotein E4
  • Biomarkers
  • DNMT3A protein, human
  • PSEN1 protein, human
  • Presenilin-1
  • Homocysteine
  • DNA
  • Folic Acid
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • DNA (Cytosine-5-)-Methyltransferase 1
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • DNMT1 protein, human
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human
  • Vitamin B 12