Researchers at the Icahn School of Medicine at Mount Sinai have made a major breakthrough in Alzheimer’s disease research, identifying a new way to slow or even stop the progression of the disease. The study, which focuses on the role of reactive astrocytes and the plexin-B1 protein in Alzheimer’s pathophysiology, provides critical insights into brain cell communication and opens the door to innovative treatment strategies. Posted on Nature Neuroscience (DOI 10.1038/s41593-024-01664-w) on 27 May.
This groundbreaking work focuses on manipulating the protein plexin-B1 to enhance the brain’s ability to clear the amyloid plaques that characterize Alzheimer’s disease. Reactive astrocytes, a type of brain cell that are activated in response to injury or disease, were found to play a critical role in this process. They help control the distance around amyloid plaques, affecting how other brain cells can access and clear these harmful deposits.
Our findings offer a promising route to developing new therapies 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 based on the analysis of complex data comparing healthy people with people with Alzheimer’s, with the aim of understanding the molecular and cellular foundations of the disease.
Hongyan Zou, PhD, Professor of Neurosurgery and Neuroscience, at Icahn Mount Sinai and one of the lead authors of the study, emphasized the broader implications of their findings:Our study opens new avenues for Alzheimer’s research, highlighting the importance of cellular interactions in the development of treatments for neurodegenerative diseases.”
One of the most important achievements of the study is the 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 disease. It lays a solid foundation for the development of new therapeutics 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 for targeted therapies to disrupt disease progression.
The research team stresses that while their findings mark an important advance in the battle 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 the progression of Alzheimer’s,” added Dr. Zhang, describing the team’s commitment to further explore 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 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 to treat and prevent Alzheimer’s disease.
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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Journal Reference:
Huang, Y., et al. (2024). Regulation of cell spacing in periplaque glial networks by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease. Nature Neuroscience. doi.org/10.1038/s41593-024-01664-w.
