Epigenetic alterations in Brain tissue and Alzheimer's Disease




Shewale, Shantanu J.
Barber, Robert C.
Planz, John


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Background: Epigenetic factors such as methylation of DNA have shown to impact the phenotype of a cell and irregular methylation of DNA has been correlated with numerous diseases. DNA methylation has been shown to impact the expression of certain genes associated with AD. Methods: A novel method, methylated DNA immunoprecipitation (MeDIP), is used to study genome wide methylation patterns via high throughput sequencing to assess DNA methylation patterns in brain tissue from individuals diagnosed with AD (N=12) and age matched controls (N=12). MeDIP isolation facilitates an unbiased methylation analysis of the entire human genome by enriching samples for methylated DNA fragments. The MethylMiner kit (Life Technologies) was utilized to precipitate methylated DNA, which was sequenced on the Illumina Hi-seq 2500. In addition, another aliquot will undergo MeDIP and bisulfite treatment. This will allow analysis of methylated cytosines at single base pair resolution across the entire genome. In addition, RNA and miRNA-seq was performed on the Illumina Hi-seq 2500. RNA-seq information obtained provides additional insight on epigenetic impacts on miRNA and RNA levels. Results: Sequence data reveal a genome wide methylation pattern profile, along with gene expression changes that differentiate case from control participants. Conclusions: These data provide insight and help explain a portion of the missing heritability that has yet to be characterized for AD.