Alzheimer's disease: Inflammation triggers fatal cycle
University of Bonn study proves disastrous contribution of an ancient immune mechanism
An immune reaction in the brain seems to play a major role in the development of Alzheimer's disease. In a way, it "adds fuel to the fire" and apparently causes an inflammation that, in a sense, keeps kindling itself. The study has now been published in the journal Cell Reports. Alzheimer's disease is characterized by clumps of the protein Aß (amyloid beta), which form large plaques in the brain. Aß resembles molecules on the surface of some bacteria. Over many millions of years, organisms have therefore developed defense mechanisms against such structures. These mechanisms are genetically determined and therefore belong to the so-called innate immune system. They usually result in certain scavenger cells absorbing and digesting the molecule.
In the brain, the microglia cells take over this role. In doing so, however, they trigger a devastating process that appears to be largely responsible for the development of dementia. On contact with Aß, certain molecule complexes, the inflammasomes, become active in the microglia cells. They then resemble a wheel with enzymes on the outside. These can activate immune messengers and thereby trigger an inflammation by directing additional immune cells to the site of action.
"Sometimes the microglia cells perish during this process," explains Prof. Dr. Michael Heneka, head of a research group at the German Center for Neurodegenerative Diseases (DZNE) and director of the Department of Neurodegenerative Diseases and Gerontopsychiatry at the University Hospital Bonn. "Then they release activated inflammasomes into their environment, the ASC specks." Prof. Michael Heneka is a member of the Cluster of Excellence ImmunoSensation.
Publication
Lea L. Friker, Hannah Scheiblich, Inga V. Hochheiser, Rebecca Brinkschulte, Dietmar Riedel, Eicke Latz, Matthias Geyer and Michael T. Heneka: Amyloid Clustering around ASC Fibrils Boosts Its Toxicity in Microglia; Cell Reports; DOI: 10.1016/j.celrep.2020.02.025
Contact
Prof. Dr. Michael Heneka
Director of the Department of Neurodegenerative Diseases and Gerontopsychiatry
University Hospital Bonn
German Center for Neurodegenerative Diseases (DZNE)
Tel. +49-(0)228-28713091
E-mail: michael.heneka@dzne.de
