Scientists are presenting fresh insights suggesting that preventing brain inflammation could be an effective strategy for addressing Alzheimer’s disease. Their research, which involved experiments using cell cultures, mice, and tissue samples from patients, could aid in creating more effective treatments. The results have been published in the scientific journal Immunity.
A team of scientists from DZNE, University Hospital Bonn (UKB), and the University of Bonn have revealed new evidence that stopping brain inflammation is a promising method for treating Alzheimer’s disease. Based on studies involving cell cultures, mice, and patient tissue samples, their findings could pave the way for more effective therapies. These results are featured in the scientific journal Immunity.
Alzheimer’s disease, recognized as the most prevalent type of dementia, is linked to protein buildup in the brain. The clustering of these proteins, referred to as “amyloid-beta,” initiates a series of events that ultimately damages neurons and results in their death. “The disease involves a complicated interplay of various mechanisms. One significant factor is neuroinflammation, which we investigated in our studies. Specifically, we altered a molecular complex known as the NLRP3 inflammasome, found in microglia—the immune cells of the brain,” explains Dr. RóisÃn McManus, a research group leader at DZNE, investigator at UKB’s Institute of Innate Immunity, and part of the “ImmunoSensation2” Cluster of Excellence at the University of Bonn.
Newly Discovered Pathways
The “NLRP3 inflammasome” acts as a regulatory switch: in the context of Alzheimer’s disease, its activation sparks an inflammatory response detrimental to neurons. Consequently, researchers are seeking methods to deactivate this molecular complex using medications. The current findings bolster this strategy. “It has been established that inhibiting NLRP3 not only diminishes neuroinflammation but also enhances the ability of microglia to remove harmful amyloid-beta deposits through a process known as phagocytosis. Our findings are novel in that they enhance understanding of the critical role NLRP3 plays in microglia and clarify the mechanism behind the benefits of its inhibition,” states McManus. “In our investigations, we identified previously unknown signaling pathways impacted by NLRP3. Notably, we discovered how NLRP3 influences nutrient utilization in microglia and how this affects genes crucial for their functionality. This is particularly relevant to their phagocytic activity. These insights could contribute to developing new dementia therapies. Ultimately, our research highlights NLRP3 as a promising target for Alzheimer’s treatment.”
Collaborative International Effort
This research project involved cooperation between the Bonn researchers and institutions including the Luxembourg Centre for Systems Biomedicine, the University of California San Diego, Technische Universität Braunschweig, Novartis Switzerland, as well as various other organizations in Europe and beyond.
