Global changes in DNA methylation in Alzheimer’s disease peripheral blood mononuclear cells

• Published in: Brain, behavior, and immunity Vol. 45; pp. 139 - 144
• Main Authors: Di Francesco, Andrea, Arosio, Beatrice, Falconi, Anastasia, Micioni Di Bonaventura, Maria Vittoria, Karimi, Mohsen, Mari, Daniela, Casati, Martina, Maccarrone, Mauro, D’Addario, Claudio
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.03.2015
• Subjects: Aged; Aged, 80 and over; Allergy and Immunology; Alzheimer Disease - genetics; Alzheimer’s disease; APOE; Apolipoprotein E4 - genetics; Case-Control Studies; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases - genetics; DNA (Cytosine-5-)-Methyltransferases - metabolism; DNA methylation; DNA Methylation - genetics; DNA Methyltransferase 3A; DNA Methyltransferase 3B; DNMT; Epigenesis, Genetic; Epigenetics; Female; Humans; Italy; Leukocytes, Mononuclear - metabolism; Male; PBMC; Peripheral markers; Psychiatry; Pyrosequencing; Severity of Illness Index; White People - genetics; Italy; DNMT; Alzheimer’s disease; Pyrosequencing; DNA methylation; Epigenetics; Peripheral markers; APOE; PBMC
• ISSN: 0889-1591; 1090-2139; 1090-2139
• DOI: 10.1016/j.bbi.2014.11.002

•DNA methylation is increased in peripheral cells of Alzheimer’s disease patients.•DNA methylation correlates with worse cognitive performances and APOE ε4 polymorphism.•Global DNA hypermethylation is a peripheral marker of Alzheimer’s disease. 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.