Mount Sinai researchers discover key role of DNA methylation in Alzheimer's disease

Mount Sinai researchers have published a study 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). 

"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, Willard T.C. Johnson Research Professor of Neurogenetics and Director of the Mount Sinai Center for Transformative Disease Modeling. "It provides a framework for future data integration at the multi-scale network level and could lead to the discovery of new targets for drug discovery in Alzheimer's disease." 

The results of this study offer a novel approach to investigating the relationship between DNA methylation and gene/protein expression, and highlight the importance of epigenetic mechanisms in human diseases such as AD. The researchers plan to extend their methods to study the methylomic variation and impacts on multiscale networks at the single-cell level, which could provide new insights into the DNA methylation profiles of individual cell types. 

Publication URL: https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12969

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About the Icahn School of Medicine at Mount Sinai 

The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the eight member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to a large and diverse patient population. 

Ranked No. 14 nationwide in National Institutes of Health funding and in the 99th percentile in research dollars per investigator according to the Association of American Medical Colleges, Icahn Mount Sinai has a talented, productive, and successful faculty. More than 3,000 full-time scientists, educators, and clinicians work within and across 34 academic departments and 44 multidisciplinary institutes, a structure that facilitates tremendous collaboration and synergy. Our emphasis on translational research and therapeutics is evident in such diverse areas as genomics/big data, virology, neuroscience, cardiology, geriatrics, and gastrointestinal and liver diseases. 

Icahn Mount Sinai offers highly competitive MD, PhD, and master’s degree programs, with current enrollment of approximately 1,300 students. It has the largest graduate medical education program in the country, with more than 2,600 clinical residents and fellows training throughout the Health System. In addition, more than 535 postdoctoral research fellows are in training within the Health System. 

A culture of innovation and discovery permeates every Icahn Mount Sinai program. Mount Sinai’s technology transfer office, one of the largest in the country, partners with faculty and trainees to pursue optimal commercialization of intellectual property to ensure that Mount Sinai discoveries and innovations translate into health care products and services that benefit the public. 

Icahn Mount Sinai’s commitment to breakthrough science and clinical care is enhanced by academic affiliations that supplement and complement the School’s programs. Through Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai. Additionally, MSIP develops research partnerships with industry leaders such as Merck & Co., AstraZeneca, Novo Nordisk, and others. 

The Icahn School of Medicine at Mount Sinai is located in New York City on the border between the Upper East Side and East Harlem, and classroom teaching takes place on a campus facing Central Park. Icahn Mount Sinai’s location offers many opportunities to interact with and care for diverse communities. Learning extends well beyond the borders of our physical campus, to the eight hospitals of the Mount Sinai Health System, our academic affiliates, and globally. 

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* Mount Sinai Health System member hospitals: The Mount Sinai Hospital; Mount Sinai Beth Israel; Mount Sinai Brooklyn; Mount Sinai Morningside; Mount Sinai Queens; Mount Sinai South Nassau; Mount Sinai West; and New York Eye and Ear Infirmary of Mount Sinai.