Mount Sinai Researchers Discover Key Role of DNA Methylation in Alzheimer’s Disease; Findings from Novel Analytic Approach Could Contribute to Discovery of New Therapeutic Targets

Researcher at The Mount Sinai Hospital / Mount Sinai School of Medicine, and colleagues, have published a study on February 22, 2023 in Alzheimer's & Dementia: The Journal of the Alzheimer's Association that sheds new light on the role of DNA methylation in Alzheimer's disease (AD). The study found that DNA methylation has a profound impact on gene and protein co-expression networks associated with AD and could lead to the discovery of new neuropathological processes and molecular mechanisms for developing novel treatments for the disease. The study was conducted using a novel analytical approach to quantify the impact of DNA methylation on gene and protein expression and a large cohort of post-mortem control, mild cognitive impaired (MCI), and AD brains from the Mount Sinai Brain Bank. The researchers profiled genome-wide methylomic variations in the parahippocampal gyrus, a region of the brain involved in a variety of functions including memory processing, and investigated the influence of these changes on mRNA and protein co-expression networks. They discovered 270 distinct differentially methylated regions (DMRs) in AD compared to normal controls and validated their key findings using an independent cohort (Religious Orders Study and Memory Assessment Project, ROSMAP). The open-access article is titled “Genome-Wide Methylomic Regulation of Multiscale Gene Networks in Alzheimer's Disease.”

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