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CIRCUITS: Whole Genome Characterization of DNA Methylation Changes in the Aged and Alzheimer’s Disease Human Brain

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Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder. Both normal aging and Alzheimer’s disease have been correlated with changes to the patterns of DNA methylation in the brain. DNA methylation is an epigenetic mark with the capacity to stably alter gene expression. The importance of changes to DNA methylation in AD has been difficult to assess. This proposed work would characterize the alterations of genome-wide DNA methylation patterns in post-mortem human neurons in the context of normal aging and AD. We also will characterize DNA methylation patterns in human neurons generated in vitro. These foundational experiments are a critical first step in understanding the epigenetic mechanisms that contribute to Alzheimer’s disease.