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
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.
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. Paper 117.
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