Altering cellular interactions around amyloid plaques may offer novel Alzheimer’s treatment strategies

New York City, [May 27, 2024] – Researchers at the Icahn School of Medicine at Mount Sinai have made a significant breakthrough in Alzheimer’s disease research by identifying a novel way to potentially slow down or even halt disease progression. The study, which focuses on the role of reactive astrocytes and the plexin-B1 protein in Alzheimer’s pathophysiology, provides crucial insights into brain cell communication and opens the door to innovative treatment strategies. It was published in Nature Neuroscience (DOI 10.1038/s41593-024-01664-w) on May 27. 

This groundbreaking work is centered on the manipulation of the plexin-B1 protein to enhance the brain’s ability to clear amyloid plaques, a hallmark of Alzheimer’s disease. Reactive astrocytes, a type of brain cell that becomes activated in response to injury or disease, were found to play a crucial role in this process. They help control the spacing around amyloid plaques, affecting how other brain cells can access and clear these harmful deposits. “Our findings offer a promising path for developing new treatments by improving how cells interact with these harmful plaques,” said Roland Friedel, PhD, Associate Professor of Neuroscience, and Neurosurgery, at Icahn Mount Sinai and a senior author of the study. The research was driven by the analysis of complex data comparing healthy individuals to those with Alzheimer’s, aiming to understand the disease’s molecular and cellular foundations.

Hongyan Zou, PhD, Professor of Neurosurgery, and Neuroscience, at Icahn Mount Sinai and one of the study’s lead authors, highlighted the broader implications of their findings: “Our study opens new pathways for Alzheimer’s research, emphasizing the importance of cellular interactions in developing neurodegenerative disease treatments.”

One of the study’s most significant achievements is its validation of multiscale gene network models of Alzheimer’s disease. “This study not only confirms one of the most important predictions from our gene network models but also significantly advances our understanding of Alzheimer’s. It lays a solid foundation for developing novel therapeutics targeting such highly predictive network models,” said Bin Zhang, PhD, Willard T.C. Johnson Research Professor of Neurogenetics at Icahn Mount Sinai and one of the study’s lead authors. By demonstrating the critical role of plexin-B1 in Alzheimer’s disease, the research underscores the potential of targeted therapies to disrupt the disease’s progression.

The research team emphasizes that while their findings mark a significant advance in the fight against Alzheimer’s, more research is needed to translate these discoveries into treatments for human patients.

“Our ultimate goal is to develop treatments that can prevent or slow down Alzheimer’s progression,” Dr. Zhang added, outlining the team’s commitment to further exploring the therapeutic potential of plexin-B1.

This study is supported by the NIH National Institute on Aging (NIA) grants U01AG046170 and RF1AG057440 and is part of the NIA-led Accelerating Medicines Partnership – Alzheimer’s Disease (AMP-AD) Target Discovery and Preclinical Validation program. This public private partnership aims to shorten the time between the discovery of potential drug targets and the development of new drugs for Alzheimer’s disease treatment and prevention.

The paper is titled “Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease.” 

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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 13th nationwide in National Institutes of Health (NIH) funding and among 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 44 academic departments and 36 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, as well as 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 2,000 clinical residents and fellows training throughout the Health System. In addition, more than 550 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 healthcare 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 the 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.