Summary: Researchers identified a novel way to potentially slow or halt Alzheimer’s progression by targeting the plexin-B1 protein. Their study shows how reactive astrocytes and plexin-B1 play crucial roles in clearing amyloid plaques. This discovery opens new pathways for Alzheimer’s treatments and emphasizes the importance of cellular interactions.
Key Facts:
- Key Protein: Targeting plexin-B1 protein can enhance the brain’s ability to clear amyloid plaques.
- Cellular Interactions: Reactive astrocytes help control the clearance of harmful deposits in the brain.
- Innovative Treatments: The study opens new pathways for developing treatments for Alzheimer’s disease.
Source: Mount Sinai Hospital
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 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.
Funding: 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.
About this Alzheimer’s disease research news
Author: Jennifer Gutierrez
Source: Mount Sinai Hospital
Contact: Jennifer Gutierrez – Mount Sinai Hospital
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease” by Roland Friedel et al. Nature Neuroscience
Abstract
Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease
Communication between glial cells has a profound impact on the pathophysiology of Alzheimer’s disease (AD). We reveal here that reactive astrocytes control cell distancing in peri-plaque glial nets, which restricts microglial access to amyloid deposits.
This process is governed by guidance receptor Plexin-B1 (PLXNB1), a network hub gene in individuals with late-onset AD that is upregulated in plaque-associated astrocytes.
Plexin-B1 deletion in a mouse AD model led to reduced number of reactive astrocytes and microglia in peri-plaque glial nets, but higher coverage of plaques by glial processes, along with transcriptional changes signifying reduced neuroinflammation.
Additionally, a reduced footprint of glial nets was associated with overall lower plaque burden, a shift toward dense-core-type plaques and reduced neuritic dystrophy.
Altogether, our study demonstrates that Plexin-B1 regulates peri-plaque glial net activation in AD.
Relaxing glial spacing by targeting guidance receptors may present an alternative strategy to increase plaque compaction and reduce neuroinflammation in AD.
