Methylation analysis of multiple genes in blood DNA of Alzheimer’s disease and healthy individuals

• Published in: Neuroscience letters Vol. 600; pp. 143 - 147
• Main Authors: Tannorella, Pierpaola, Stoccoro, Andrea, Tognoni, Gloria, Petrozzi, Lucia, Salluzzo, Maria Grazia, Ragalmuto, Alda, Siciliano, Gabriele, Haslberger, Alexander, Bosco, Paolo, Bonuccelli, Ubaldo, Migliore, Lucia, Coppedè, Fabio
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 23.07.2015
• Subjects: 5' Untranslated Regions; Age Factors; Aged; Aged, 80 and over; Alzheimer Disease - blood; Alzheimer’s disease; Amyloid Precursor Protein Secretases - blood; Amyloid Precursor Protein Secretases - genetics; APOE; Apolipoprotein E4 - blood; Apolipoprotein E4 - genetics; Aspartic Acid Endopeptidases - blood; Aspartic Acid Endopeptidases - genetics; BACE1; Biomarkers - blood; Case-Control Studies; CpG Islands; DNA (Cytosine-5-)-Methyltransferase 1; DNA (Cytosine-5-)-Methyltransferases - blood; DNA (Cytosine-5-)-Methyltransferases - genetics; DNA - blood; DNA Methylation; DNA Methyltransferase 3A; DNA Methyltransferase 3B; DNMTs; Female; Folate; Folic Acid - blood; Homocysteine; Homocysteine - blood; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2) - blood; Methylenetetrahydrofolate Reductase (NADPH2) - genetics; MTHFR; Presenilin-1 - blood; Presenilin-1 - genetics; Promoter Regions, Genetic; PSEN1; Sex Factors; Vitamin B 12 - blood; Vitamin B12; BACE1; DNMTs; Alzheimer’s disease; DNA methylation; MTHFR; PSEN1; APOE; Homocysteine; Vitamin B12; Folate
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2015.06.009

•We studied DNA methylation levels of six candidate AD genes.•No difference in DNA methylation levels between AD and control blood DNA was found.•MTHFR methylation levels correlate with biomarkers of one-carbon metabolism. 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.