Faculty Publications and Presentations
Publication Date
2013
Document Type
Article
Disciplines
Biochemistry | Biology | Genetics | Medical Biochemistry | Medical Genetics | Medical Molecular Biology | Medical Neurobiology | Medical Pathology | Molecular and Cellular Neuroscience | Molecular Biology | Molecular Genetics | Nervous System Diseases | Neurology | Neurosciences | Pathology
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. We isolated the DNA from neurons treated with Aβ or vehicle, and digested the two samples 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.
Recommended Citation
Isaacs, Gary D.; Taher, Noor; McKenzie, Courtney; Garrett, Rebecca; Baker, Matthew; and Fox, Nena, "Aβ Alters the DNA Methylation Status of Cell-fate Genes in an Alzheimer’s Disease Model" (2013). Faculty Publications and Presentations. 117.
https://digitalcommons.liberty.edu/bio_chem_fac_pubs/117
Included in
Biochemistry Commons, Biology Commons, Genetics Commons, Medical Biochemistry Commons, Medical Genetics Commons, Medical Molecular Biology Commons, Medical Neurobiology Commons, Medical Pathology Commons, Molecular and Cellular Neuroscience Commons, Molecular Biology Commons, Molecular Genetics Commons, Nervous System Diseases Commons, Neurology Commons, Neurosciences Commons, Pathology Commons
Comments
Reprinted from Journal of Alzheimer’s Disease, Volume 38, Number 4. Noor Taher, Courtney McKenzie, Rebecca Garrett, Matthew Baker, Nena Fox, and Gary D. Isaacs. “Amyloid-β Alters the DNA Methylation Status of Cell-fate Genes in an Alzheimer’s Disease Model.” Copyright 2013, with permission from IOS Press.
IOS Press: www.iospress.nl.
Journal of Alzheimer’s Disease: http://www.iospress.nl/journal/journal-of-alzheimers-disease/.