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.

Global changes in DNA methylation in Alzheimer's disease peripheral blood mononuclear cells / A. Di Francesco, B. Arosio, A. Falconi, M.V.M. Di Bonaventura, M. Karimi, D. Mari, M. Casati, M. Maccarrone, C. D'Addario. - In: BRAIN BEHAVIOR AND IMMUNITY. - ISSN 0889-1591. - 45(2015), pp. 1-6. [Epub ahead of print] [10.1016/j.bbi.2014.11.002]

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

B. Arosio
Secondo
;
D. Mari;M. Casati;
2015

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.
APOE; Alzheimer’s disease; DNA methylation; DNMT; Epigenetics; PBMC; Peripheral markers; Pyrosequencing
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
Article (author)
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0889159114005170-main.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 826.63 kB
Formato Adobe PDF
826.63 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/250758
Citazioni
  • ???jsp.display-item.citation.pmc??? 50
  • Scopus 91
  • ???jsp.display-item.citation.isi??? 87
social impact