title: Artificial Neural Networks Link One-Carbon Metabolism to Gene-Promoter Methylation in Alzheimer's Disease.
abstract: 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.
  
  
  
  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.
  
  
  
  We applied a data mining system called Auto Contractive Map to an existing database of 100 AD and 100 control individuals.
  
  
  
  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.
  
  
  
  The present pilot study suggests that promoter methylation levels of the studied genes are linked to circulating levels of folates, hcy, and vitamin B12.
authors.affiliation: Villa Santa Maria Institute, Tavernerio, Italy.|Semeion Research Center of Sciences of Communication, Rome, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Grossi
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Section of Medical Genetics, University of Pisa, Pisa, Italy.|Doctoral School in Genetics, Oncology, and Clinical Medicine, University of Siena, Siena, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Stoccoro
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Section of Medical Genetics, University of Pisa, Pisa, Italy.
authors.forename: Pierpaola
authors.initials: P
authors.lastname: Tannorella
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Section of Medical Genetics, University of Pisa, Pisa, Italy.|Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, Pisa, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Migliore
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Section of Medical Genetics, University of Pisa, Pisa, Italy.|Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, Pisa, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Coppedè
mesh_terms: D000367:Age Factors; D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D016571:Neural Networks, Computer; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012737:Sex Factors; D014805:Vitamin B 12 / Q000097:blood
chemical_list: D015415:Biomarkers; C508853:PSEN1 protein, human; D053764:Presenilin-1; D006710:Homocysteine; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D004248:DNA (Cytosine-5-)-Methyltransferases; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D014805:Vitamin B 12
keywords: Alzheimer’s disease; BACE1; DNA methylation; DNMT; MTHFR; PSEN1; folate; homocysteine; vitamin B12