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Article type: Research Article
Authors: Taher, Noora | McKenzie, Courtneya; 1 | Garrett, Rebeccaa; 1 | Baker, Matthewa; 1 | Fox, Nenab | Isaacs, Gary D.a; *
Affiliations: [a] Department of Biology and Chemistry, Liberty University, Lynchburg, VA, USA | [b] University of Virginia School of Medicine, Tissue Culture Facility, Charlottesville, VA, USA
Correspondence: [*] Correspondence to: Gary D. Isaacs, Ph.D., 1971 University Boulevard, Lynchburg, VA 24502, USA. Tel.: +1 434 582 2224; Fax: +1 434 582 2488; E-mail: [email protected].
Note: [1] These authors contributed equally to this work.
Abstract: Alzheimer's disease (AD) is characterized by neurofibrillary tangles and extracellular amyloid-β plaques (Aβ). Despite ongoing research, some ambiguity remains surrounding the role of Aβ in the pathogenesis of this neurodegenerative disease. While several studies have focused on the mutations associated with AD, our understanding of the epigenetic contributions to the disease remains less clear. To that end, we determined the changes in DNA methylation in differentiated human neurons with and without Aβ treatment. DNA was isolated from neurons treated with Aβ or vehicle, and the two samples were digested with either a methylation-sensitive (HpaII) or a methylation-insensitive (MspI) restriction endonuclease. The fragments were amplified and co-hybridized to a commercial promoter microarray. Data analysis revealed a subset of genomic loci that shows a significant change in DNA methylation following Aβ treatment in comparison to the control group. After mapping these loci to nearby genes, we discovered high enrichment for cell-fate genes that control apoptosis and neuronal differentiation. Finally, we incorporated three of those genes in a possible model suggesting the means by which Aβ contributes to the brain shrinkage and memory loss seen in AD.
Keywords: Alzheimer's disease, amyloid-β fragment 1-40, DNA methylation, neurogenesis
DOI: 10.3233/JAD-131061
Journal: Journal of Alzheimer's Disease, vol. 38, no. 4, pp. 831-844, 2014
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