June 18, 2024

New Study Uncovers Genetic Changes in Brain Cells Linked to Neuroinflammation in Alzheimer’s

A recent study conducted by researchers from Brigham and Women’s Hospital (BWH) has shed light on the genetic changes occurring in a specific group of brain cells, known as microglia, that contribute to neuroinflammation and ultimately to the development and progression of Alzheimer’s disease (AD). This groundbreaking research could potentially lead to the development of more targeted and effective therapeutics for the treatment of AD.

Microglia are specialized immune-regulating cells in the brain that have been found to play crucial roles in both healthy and diseased brains. However, the molecular mechanisms underlying the relationship between microglia and neuroinflammation in AD have remained largely unknown. The study aimed to uncover these pathways and investigate how genetic changes in microglia contribute to neuroinflammation and AD.

“We know that microglia play important roles in the healthy and diseased brain, but, in many cases, the molecular mechanisms underlying this relationship are poorly understood,” said Tracy Young-Pearse, the corresponding author of the study. “If we’re able to identify and understand the significance of specific genes that play a role in neuroinflammation, we can more readily develop effective, targeted therapeutics.”

The researchers focused on the inositol polyphosphate-5-phosphatase D (INPP5D) gene, which previous studies had linked to an increased risk of AD. Analyzing brain tissue samples from AD patients, the researchers observed conflicting results. While the levels of the INPP5D gene were elevated in AD and associated with the presence of amyloid beta plaque-associated microglia, the levels of the INPP5D protein were significantly reduced. This suggested that, despite the increased number of genes, the INPP5D protein was not functioning properly.

To further investigate this phenomenon, the researchers studied living human brain cells derived from stem cells. They discovered certain proteins that were involved in the inflammatory process when the activity of the INPP5D gene was reduced. These proteins could potentially be targeted to block inflammasome activation in microglia. Inflammasomes are receptors/sensors in the innate immune system that trigger inflammatory responses.

Although the study provides promising insights, it remains to be determined whether INPP5D can be targeted for therapeutic purposes. The findings indicate that the activity of INPP5D in AD brains is complex, necessitating further research to understand if targeting INPP5D could prevent the cognitive decline associated with the disease. “Our results highlight an exciting promise for INPP5D, but some questions still remain,” said Young-Pearse. “Future studies examining the interaction between INPP5D activity and inflammasome regulation are essential to improve our understanding of microglia in AD and to help develop a comprehensive toolbox of therapeutics that can be deployed to treat the various molecular pathways leading to AD.”

In conclusion, the recent study conducted by BWH researchers has provided valuable insights into the genetic changes occurring in microglia that contribute to neuroinflammation in Alzheimer’s disease. This research has the potential to pave the way for the development of targeted therapeutics that can effectively alleviate the neuroinflammation and cognitive decline associated with AD. Further investigations are needed to fully comprehend the role of the INPP5D gene and its potential as a therapeutic target in AD.

1. Source: Coherent Market Insights, Public sources, Desk research
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