A recent study conducted by researchers at Brigham and Women’s Hospital sheds light on the role of genetic changes in microglia, immune-regulating brain cells, and their contribution to neuroinflammation leading to Alzheimer’s disease (AD). Published in Nature Communications, the findings reveal that a decrease in the INPP5D gene within microglia is associated with increased neuroinflammation and heightened Alzheimer’s disease risk.
Tracy Young-Pearse, PhD, the corresponding author from the Department of Neurology at Brigham and Women’s Hospital, emphasized the significance of understanding the molecular mechanisms underlying the relationship between microglia and brain health. The study’s focus on specific genes involved in neuroinflammation aims to pave the way for targeted therapeutic interventions.
Neuroinflammation is a crucial factor in neurodegenerative diseases like AD, yet its early detection proves challenging. The research highlights the pivotal role of microglia in neuroinflammation but underscores the need for a deeper understanding of the molecular pathways involved.
The research team employed various experimental approaches, including the examination of human brain tissue from AD patients and a control group. Lower levels of INPP5D were identified in AD patients, correlating with activated inflammation. Additionally, the team used human brain cells derived from stem cells to explore molecular interactions within microglia, revealing specific proteins that could be targeted to inhibit inflammasome activation.
While the study represents a comprehensive analysis of INPP5D in the AD brain, the researchers caution that the complex nature of INPP5D activity in AD brains requires further investigation. The potential therapeutic targeting of INPP5D remains an open question, and the researchers stress the need for future studies to determine if such targeting could prevent cognitive decline in AD patients.
Young-Pearse expressed optimism about the promising aspects of INPP5D but acknowledged that key questions persist. Future studies, she notes, are crucial to unravel the intricate interplay between INPP5D activity and inflammasome regulation, providing a more nuanced understanding of microglia in AD and aiding in the development of a comprehensive toolbox of therapeutics targeting diverse molecular pathways leading to AD.
