Epigenetic modifications to cytosine have been shown to regulate transcription in cancer, embryonic development, and recently neurodegeneration. While cytosine methylation studies are now common in neurodegenerative research, hydroxymethylation studies are rare, particularly genome-wide mapping studies. As an initial study to analyze 5-hydroxymethylcytosine (5-hmC) in the Alzheimer’s disease (AD) genome, reduced representation hydroxymethylation profiling (RRHP) was used to analyze more than 2 million sites of possible modification in hippocampal DNA of sporadic AD and normal control subjects. Genes with differentially hydroxymethylated regions were filtered based on previously published microarray data for altered gene expression in hippocampal DNA of AD subjects. Our data show significant pathways for altered levels of 5-hmC in the hippocampus of AD subjects compared to age-matched normal controls involved in signaling, energy metabolism, cell function, gene expression, protein degradation, and cell structure and stabilization. Overall, our data suggest a possible role for the dysregulation of epigenetic modifications to cytosine in late stage AD.

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Published in Journal of Molecular Neuroscience, v. 63, issue 2, p. 185-197.

© Springer Science+Business Media, LLC 2017

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This is a post-peer-review, pre-copyedit version of an article published in Journal of Molecular Neuroscience. The final authenticated version is available online at: https://doi.org/10.1007/s12031-017-0969-y

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This research was supported by National Institutes of Health grant P30-AG028383 and by a grant from the office of the Vice President for Research of the University of Kentucky.

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The online version of this article (https://doi.org/10.1007/s12031-017-0969-y) contains supplementary material, which is available to authorized users.