期刊
BRAIN BEHAVIOR AND IMMUNITY
卷 45, 期 -, 页码 139-144出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2014.11.002
关键词
Alzheimer's disease; APOE; DNA methylation; DNMT; Epigenetics; PBMC; Peripheral markers; Pyrosequencing
资金
- Italian Ministry of Education , University and Research [FIRB-RBFR12DELS]
- Fondazione TERCAS-Progetto Speciale Assegni di Ricerca
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 (DNMTI) 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 epsilon 4 allele (p = 0.0043) in the global population. Among the APOE epsilon 3 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. (C) 2014 Elsevier Inc. reserved.
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