Laboratory findings support the concept that reduction in neuroinflammation could help Alzheimer’s fight

Insights into immune cells in the context of neurodegeneration

Scientists from a German state research organisation that studies the causes of diseases of the central nervous system – the DZNE – with University Hospital Bonn (UKB) and the University of Bonn have provided new evidence that preventing brain inflammation is a promising approach for the treatment of Alzheimer’s disease, based on studies in cell culture, mice and tissue samples from patients.

Alzheimer’s disease, which is the most common form of dementia, is associated with deposits of proteins in the brain. The aggregation of these proteins, which are known as ‘amyloid-beta,’ gives rise to a sequence of events that ultimately harms neurons and leads to their loss.

“Alzheimer’s disease involves a complex interaction of different mechanisms. One of these is neuroinflammation – which we looked at in our research,” said Dr. Róisín McManus, a DZNE research group leader, investigator at UKB’s Institute of Innate Immunity and also a member of the ‘ImmunoSensation2’ Cluster of Excellence at the University of Bonn.

“Specifically, we pharmacologically manipulated a molecular complex called the NLRP3 inflammasome. It is found in microglia, which are the immune cells of the brain,” she said.

The ‘NLRP3 inflammasome’ is like a control switch. In Alzheimer’s disease, its activation triggers an inflammatory response that harms neurons. For this reason, researchers have been exploring ways to inactivate this molecular complex using drugs. The current results support this approach.

“It is known that inhibiting NLRP3 not only reduces neuroinflammation, but also helps microglia clear the harmful amyloid-beta deposits, a process called phagocytosis.

“The novelty of our findings is that they provide a better understanding of the important role that NLRP3 plays in microglia and will also unravel the mechanism behind why its inhibition is so beneficial,” added McManus.

“In our studies we have identified previously unknown signalling pathways influenced by NLRP3. In particular, we found that NLRP3 regulates how microglia use nutrients and how these act on genes that have a major impact on the function of microglia. This is very relevant for their ability to carry out phagocytosis.

“These findings could help in the development of therapies for dementia. In any case, our research shows that NLRP3 is a promising target for the treatment of Alzheimer’s disease,” she added.

In this project, the Bonn-based researchers also collaborated with the Luxembourg Centre for Systems Biomedicine, University of California San Diego, Technische Universität Braunschweig, Novartis Switzerland and other institutions in Europe and around the world.

For further reading please visit: 10.1016/j.immuni.2025.01.007