Modifying Cellular Interactions Near Amyloid Plaques May Offer New Alzheimer's Treatments

Researchers at Mount Sinai’s Icahn School of Medicine have achieved a big breakthrough in Alzheimer’s disease research by discovering a new technique to slow or even stop disease development. The study, which focuses on the involvement of reactive astrocytes and the plexin-B1 protein in Alzheimer’s pathology, sheds light on brain cell communication and opens the door to novel treatment techniques. The study was published in Nature Neuroscience.

This revolutionary study focuses on manipulating the plexin-B1 protein to improve the brain’s capacity to eliminate amyloid plaques, a hallmark of Alzheimer's disease. Reactive astrocytes, a kind of brain cell that activates in response to damage or sickness, were discovered to play an important part in this process.

They assist in managing the spacing surrounding amyloid plaques, which affects how other brain cells can access and remove these toxic deposits.

Our findings offer a promising path for developing new treatments by improving how cells interact with these harmful plaques.”

Roland Friedel, PhD, Study Senior Author and Associate Professor, Department of Neuroscience and Neurosurgery, The Mount Sinai Hospital

The study was motivated by the examination of complicated data comparing healthy individuals with those with Alzheimer’s disease, with the goal of better understanding the disease’s molecular and cellular foundations.

Our study opens new pathways for Alzheimer’s research, emphasizing the importance of cellular interactions in developing neurodegenerative disease treatments.”

Hongyan Zou, PhD, Study Lead Author and Professor, Department of Neurosurgery and Neuroscience, The Mount Sinai Hospital

One of the study’s most notable accomplishments was 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. It lays a solid foundation for developing novel therapeutics targeting such highly predictive network models.”

Bin Zhang, PhD, Study Lead Author and Research Professor, Department of Neurogenetics, Willard T.C. Johnson, The Mount Sinai Hospital

The study highlights the significance of plexin-B1 in Alzheimer’s disease and the possibility of using targeted drugs to halt the disease’s progression.

Although the research team’s results represent a major advancement in the battle against Alzheimer’s, they stress that further study is necessary before these findings can be used to develop therapies for actual patients.

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

Source:
Journal reference:

Huang, Y., et al. (2024) Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease. Nature Neuroscience. doi.org/10.1038/s41593-024-01664-w

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