Artificial Neural Networks Link One-Carbon Metabolism to Gene-Promoter Methylation in Alzheimer's Disease

J Alzheimers Dis. 2016 Jul 1;53(4):1517-22. doi: 10.3233/JAD-160210.

Abstract

Background: There is increasing interest in DNA methylation studies in Alzheimer's disease (AD), but little is still known concerning the relationship between gene-promoter methylation and circulating biomarkers of one-carbon metabolism in patients.

Objective: To detect the connections among circulating folate, homocysteine (hcy) and vitamin B12 levels and promoter methylation levels of PSEN1, BACE1, DNMT1, DNMT3A, DNMT3B, and MTHFR genes in blood DNA.

Methods: We applied a data mining system called Auto Contractive Map to an existing database of 100 AD and 100 control individuals.

Results: Low vitamin B12 was linked to the AD condition, to low folates, and to high hcy. Low PSEN1 methylation was linked to low folate levels as well as to low promoter methylation of BACE1 and DNMTs genes. Low hcy was linked to controls, to high folates and vitamin B12, as well as to high methylation levels of most of the studied genes.

Conclusions: The present pilot study suggests that promoter methylation levels of the studied genes are linked to circulating levels of folates, hcy, and vitamin B12.

Keywords: Alzheimer’s disease; BACE1; DNA methylation; DNMT; MTHFR; PSEN1; folate; homocysteine; vitamin B12.

MeSH terms

  • Age Factors
  • Aged
  • Alzheimer Disease / blood*
  • Alzheimer Disease / genetics*
  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid Precursor Protein Secretases / metabolism
  • Aspartic Acid Endopeptidases / genetics
  • Aspartic Acid Endopeptidases / metabolism
  • Biomarkers / blood
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Methylation*
  • Female
  • Folic Acid / blood
  • Homocysteine / blood
  • Humans
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Methylenetetrahydrofolate Reductase (NADPH2) / metabolism
  • Neural Networks, Computer
  • Presenilin-1 / genetics
  • Presenilin-1 / metabolism
  • Promoter Regions, Genetic*
  • Sex Factors
  • Vitamin B 12 / blood

Substances

  • Biomarkers
  • PSEN1 protein, human
  • Presenilin-1
  • Homocysteine
  • Folic Acid
  • MTHFR protein, human
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • DNA (Cytosine-5-)-Methyltransferases
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human
  • Vitamin B 12