title: Global changes in DNA methylation in Alzheimer's disease peripheral blood mononuclear cells.
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.
authors.affiliation: Faculty of Bioscience and Technology for Food Agriculture and Environment, University of Teramo, Teramo, Italy. Electronic address: adifra@hotmail.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Di Francesco
authors.affiliation: Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, Milan, Italy; Fondazione Ca' Granda, IRCCS, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Arosio
authors.affiliation: Faculty of Bioscience and Technology for Food Agriculture and Environment, University of Teramo, Teramo, Italy.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Falconi
authors.affiliation: School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, MC, Italy.
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Micioni Di Bonaventura
authors.affiliation: Center for Hematology and Regenerative Medicine (HERM), Department of Medicine Huddinge, Karolinska Institute, Stockholm, Sweden.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Karimi
authors.affiliation: Geriatric Unit, Department of Medical Sciences and Community Health, University of Milan, Milan, Italy; Fondazione Ca' Granda, IRCCS, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Mari
authors.affiliation: Fondazione Ca' Granda, IRCCS, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Casati
authors.affiliation: Center of Integrated Research, Campus Bio-Medico University of Rome, Italy; European Center for Brain Research, Santa Lucia Foundation, IRCCS, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
authors.affiliation: Faculty of Bioscience and Technology for Food Agriculture and Environment, University of Teramo, Teramo, Italy; Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: cdaddario@unite.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: D'Addario
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D016022:Case-Control Studies; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D007558:Italy; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D012720:Severity of Illness Index; D044465:White People / Q000235:genetics; D000097584:DNA Methyltransferase 3B
chemical_list: D053327:Apolipoprotein E4; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C000619380:DNMT1 protein, human
keywords: APOE; Alzheimer’s disease; DNA methylation; DNMT; Epigenetics; PBMC; Peripheral markers; Pyrosequencing