Alzheimer’s Breakthrough: Researchers Discover Novel Way To Potentially Halt Disease Progression

Glowing Red Neuron Dementia

Mount Sinai researchers have discovered a potential new method to treat Alzheimer’s by targeting the plexin-B1 protein to improve plaque clearance in the brain, opening avenues for future therapeutic strategies. Credit:

Innovative research from Mount Sinai has also identified new pathways for research.

Researchers at the Icahn School of Medicine at Mount Sinai have achieved a major breakthrough in Alzheimer’s disease research. Their study identifies a promising method that could potentially slow or even stop the progression of the disease. Focusing on the role of reactive astrocytes and the plexin-B1 protein in Alzheimer’s disease, the research offers vital insights into how brain cells communicate. This opens up new avenues for innovative treatment approaches. The findings were published on May 27 in the journal Nature Neuroscience.

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.

PLXNB1 in AD Graphic

Icahn Mount Sinai researchers find PLXNB1, a hub gene predicted to drive a gene subnetwork causally linked to human AD, is upregulated in reactive astrocytes surrounding amyloid plaques. Credit: Bin Zhang, PhD, Icahn Mount Sinai

Broad Implications and Validation of Gene Network Models

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.

Reference: “Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease” by Yong Huang, Minghui Wang, Haofei Ni, Jinglong Zhang, Aiqun Li, Bin Hu, Chrystian Junqueira Alves, Shalaka Wahane, Mitzy Rios de Anda, Lap Ho, Yuhuan Li, Sangjo Kang, Ryan Neff, Ana Kostic, Joseph D. Buxbaum, John F. Crary, Kristen J. Brennand, Bin Zhang, Hongyan Zou and Roland H. Friedel, 27 May 2024, Nature Neuroscience.
DOI: 10.1038/s41593-024-01664-w

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.

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