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DNA Methylation Influences Gene, Protein Expression Networks in Alzheimer Disease
DNA methylation has a profound impact on the gene and protein co-expression networks underlying Alzheimer disease, according to study results published online ahead of print in Alzheimer's & Dementia.
“Our study represents the first comprehensive effort to integrate high-throughput profiling of multi-omics in Alzheimer’s disease,” said senior author Bin Zhang, PhD, a neurogenetics research professor and director of the Mount Sinai Center for Transformative Disease Modeling in New York, New York. “It provides a framework for future data integration at the multiscale network level and could lead to the discovery of new targets for drug discovery in Alzheimer’s disease.”
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Researchers looked at the impact of DNA methylation on gene and protein expression in 201 post-mortem brains from control subjects and people with mild cognitive impairment and Alzheimer disease. Specifically, the team profiled genome-wide methylomic variations in the parahippocampal gyrus, a brain region involved in memory processing and other functions, and investigated the effect of the changes on mRNA and protein co-expression networks.
The study revealed 270 distinct differentially methylated regions in the brains of people with Alzheimer disease compared with control subjects.
“A metric was developed to quantify methylation impact on each gene and each protein,” researchers reported. “DNA methylation was found to have a profound impact on not only the Alzheimer disease-associated gene modules but also key regulators of the gene and protein networks.”
The research team validated its key findings in an independent multi-mics cohort with Alzheimer disease.
“The quantified impact of DNA methylation on gene and protein networks underlying Alzheimer’s disease identified potential upstream epigenetic regulators of Alzheimer’s disease,” researchers wrote.
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