In a new study, researchers found that inflammation drives the progression of neurodegenerative brain diseases and plays a major role in the accumulation of tau proteins within neurons.
The findings are based on the analyses of human brain tissue and further lab studies. In the particular case of Alzheimer’s the results reveal a hitherto unknown connection between Abeta and tau pathology.
Furthermore, the results indicate that inflammatory processes represent a potential target for future therapies.
The research was conducted by an international team led by the German Center for Neurodegenerative Diseases (DZNE) and the University of Bonn.
Tau proteins usually stabilize a neuron’s skeleton.
However, in Alzheimer’s disease, frontotemporal dementia (FTD), and other “tauopathies,” these proteins are chemically altered, they detach from the cytoskeleton and stick together.
As a result, the cell’s mechanical stability is compromised to such an extent that it dies off. In essence, “tau pathology” gives neurons the deathblow.
The current study provides new insights into why tau proteins are transformed. As it turns out, inflammatory processes triggered by the brain’s immune system are a driving force.
The team found that a particular protein complex, the “NLRP3 inflammasome,” plays a central role in these processes.
This macromolecule is located inside the brain’s immune cells. It is a molecular switch that can trigger the release of inflammatory substances.
The researchers examined tissue samples from the brains of deceased FTD patients, cultured brain cells, and mice that exhibited hallmarks of Alzheimer’s and FTD.
The results showed that the inflammasome and the inflammatory reactions it triggers play an important role in the emergence of tau pathology.
In particular, the researchers discovered that the inflammasome influences enzymes that induce a chemical change of tau proteins.
This chemical change ultimately causes them to separate from the scaffold of neurons and clump together.
The team says the inflammasome plays a key role in Alzheimer’s and other brain diseases.
With these findings, the team sees opportunities for new treatment methods.
Future drugs could tackle exactly this by modulating the immune response. With the development of tau pathology, mental abilities decline more and more.
The lead author of the study is Prof. Michael Heneka.
The study is published in Nature.
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