title: Methylation analysis of multiple genes in blood DNA of Alzheimer's disease and healthy individuals.
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.
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Section of Medical Genetics, University of Pisa, Via Roma 55, Pisa 56126, Italy; Department of Biology, University of Pisa, Via Luca Ghini 13, Pisa 56126, 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, Via Roma 55, Pisa 56126, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Stoccoro
authors.affiliation: Unit of Neurology, Department of Neuroscience, Pisa University Hospital, Via Roma 67, Pisa 56126, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Tognoni
authors.affiliation: Unit of Neurology, Department of Neuroscience, Pisa University Hospital, Via Roma 67, Pisa 56126, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Petrozzi
authors.affiliation: IRCCS, Oasi Maria SS Institute for Research on Mental Retardation and Brain Aging, Via Conte Ruggero 73, 94018 Troina, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Salluzzo
authors.affiliation: IRCCS, Oasi Maria SS Institute for Research on Mental Retardation and Brain Aging, Via Conte Ruggero 73, 94018 Troina, Italy.
authors.forename: Alda
authors.initials: A
authors.lastname: Ragalmuto
authors.affiliation: Unit of Neurology, Department of Neuroscience, Pisa University Hospital, Via Roma 67, Pisa 56126, Italy; Department of Clinical and Experimental Medicine, University of Pisa, Neurological Clinic, Via Roma 67, Pisa 56126, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
authors.affiliation: Department of Nutritional Sciences, University of Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Haslberger
authors.affiliation: IRCCS, Oasi Maria SS Institute for Research on Mental Retardation and Brain Aging, Via Conte Ruggero 73, 94018 Troina, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bosco
authors.affiliation: Unit of Neurology, Department of Neuroscience, Pisa University Hospital, Via Roma 67, Pisa 56126, Italy; Department of Clinical and Experimental Medicine, University of Pisa, Neurological Clinic, Via Roma 67, Pisa 56126, Italy.
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Bonuccelli
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Section of Medical Genetics, University of Pisa, Via Roma 55, Pisa 56126, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, Via del Borghetto 80, Pisa 56124, 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, Via Roma 55, Pisa 56126, Italy; Interdepartmental Research Center Nutrafood "Nutraceuticals and Food for Health", University of Pisa, Via del Borghetto 80, Pisa 56124, Italy. Electronic address: fabio.coppede@med.unipi.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Coppedè
mesh_terms: D020121:5' Untranslated Regions; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood*; D053829:Amyloid Precursor Protein Secretases / Q000097:blood / Q000235:genetics; D053327:Apolipoprotein E4 / Q000097:blood / Q000235:genetics; D016282:Aspartic Acid Endopeptidases / Q000097:blood / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018899:CpG Islands; D004247:DNA / Q000097:blood*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000097:blood / Q000235:genetics; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000097:blood / Q000235:genetics; D053764:Presenilin-1 / Q000097:blood / Q000235:genetics; D011401:Promoter Regions, Genetic; D012737:Sex Factors; D014805:Vitamin B 12 / Q000097:blood; D000097584:DNA Methyltransferase 3B
chemical_list: D020121:5' Untranslated Regions; D053829:Amyloid Precursor Protein Secretases; D053327:Apolipoprotein E4; D016282:Aspartic Acid Endopeptidases; D015415:Biomarkers; D004247:DNA; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D005492:Folic Acid; D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D053764:Presenilin-1; D014805:Vitamin B 12; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C508853:PSEN1 protein, human; C573423:MTHFR protein, human; C000619380:DNMT1 protein, human; C509280:BACE1 protein, human
keywords: APOE; Alzheimer’s disease; BACE1; DNA methylation; DNMTs; Folate; Homocysteine; MTHFR; PSEN1; Vitamin B12