Researchers identify new way to potentially slow or stop progression of Alzheimer's disease

Researchers at the Icahn School of Medicine at Mount Sinai have made a significant advance in Alzheimer's disease research by identifying a new way to potentially slow or even stop the progression of the disease. The study, which focuses on the role of reactive astrocytes and the protein plexin-B1 in the pathophysiology of Alzheimer's disease, provides crucial information on communication between brain cells and opens the door to treatment strategies innovative. It was published in Natural neuroscience (DOI 10.1038/s41593-024-01664-w) on May 27.

This groundbreaking work centers on manipulating the protein plexin-B1 to improve the brain's ability to clear amyloid plaques, a hallmark of Alzheimer's disease. Reactive astrocytes, a type of brain cell that activates in response to injury or disease, play a crucial role in this process. They help control the spacing around amyloid plaques, thereby affecting how other brain cells can access and remove these harmful deposits.

Our results offer a promising avenue for developing new treatments by improving the way cells interact with these harmful plaques. »

Roland Friedel, PhD, associate professor of neuroscience and neurosurgery, at Icahn Mount Sinai and senior author of the study

The research was driven by the analysis of complex data comparing healthy individuals to those with Alzheimer's disease, with the aim of understanding the molecular and cellular underpinnings of the disease.

Hongyan Zou, PhD, professor of neurosurgery and neuroscience at Icahn Mount Sinai and one of the lead authors of the study, highlighted the broader implications of their findings: “Our study opens new avenues for Alzheimer's disease research, highlighting the importance of cellular interactions in the development of treatments against neurodegenerative diseases.

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

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

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

This study is supported by NIH National Institute on Aging (NIA) Grants U01AG046170 and RF1AG057440 and is part of the NIA-led 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 the treatment and prevention of Alzheimer's disease.

The article is titled “Regulation of cell distance in peri-plaque glial networks by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer's disease.” »