科研之友
微信
新浪微博
Facebook
分享链接
摘要
Alzheimer's disease (AD) is characterized by neurofibrillary tangles and extracellular amyloid-beta plaques (A beta). Despite ongoing research, some ambiguity remains surrounding the role of A beta 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 A beta treatment. DNA was isolated from neurons treated with A beta 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 A beta 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 A beta contributes to the brain shrinkage and memory loss seen in AD.
- 出版日期2014
