Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-09

AUTHORS

Philip L De Jager, Gyan Srivastava, Katie Lunnon, Jeremy Burgess, Leonard C Schalkwyk, Lei Yu, Matthew L Eaton, Brendan T Keenan, Jason Ernst, Cristin McCabe, Anna Tang, Towfique Raj, Joseph Replogle, Wendy Brodeur, Stacey Gabriel, High S Chai, Curtis Younkin, Steven G Younkin, Fanggeng Zou, Moshe Szyf, Charles B Epstein, Julie A Schneider, Bradley E Bernstein, Alex Meissner, Nilufer Ertekin-Taner, Lori B Chibnik, Manolis Kellis, Jonathan Mill, David A Bennett

ABSTRACT

We used a collection of 708 prospectively collected autopsied brains to assess the methylation state of the brain's DNA in relation to Alzheimer's disease (AD). We found that the level of methylation at 71 of the 415,848 interrogated CpGs was significantly associated with the burden of AD pathology, including CpGs in the ABCA7 and BIN1 regions, which harbor known AD susceptibility variants. We validated 11 of the differentially methylated regions in an independent set of 117 subjects. Furthermore, we functionally validated these CpG associations and identified the nearby genes whose RNA expression was altered in AD: ANK1, CDH23, DIP2A, RHBDF2, RPL13, SERPINF1 and SERPINF2. Our analyses suggest that these DNA methylation changes may have a role in the onset of AD given that we observed them in presymptomatic subjects and that six of the validated genes connect to a known AD susceptibility gene network. More... »

PAGES

1156-1163

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nn.3786

    DOI

    http://dx.doi.org/10.1038/nn.3786

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1037762791

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/25129075


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