In the brains of Alzheimer patients deposits of patholgical amyloid-beta protein, so-called amyloid plaques, are found. Since amyloid-beta protein plays a key role in the pathogenesis of Alzheimer's disease, research on the formation and the clearance of amyloid-beta protein is crucial for a further understanding of the disease and therefore an important prerequisite for new approaches to the treatment of Morbus Alzheimer.
Microglia cells are phagocytes (scavenger cells) that exercise monitoring functions in the brain. It has been known for a long time that in Alzheimer brains an increased clustering of microglia cells are found in immediate vicinity to amyloid plaques. Thus, microglia cells were, until now, assumed to be involved in the clearance of amyloid deposits.
In collaboration with colleagues in Berlin the scientists from Tübingen managed to develop a transgenic mouse model in which microglia cells can, for the first time, be nearly completely removed (95%). This was done by introducing a so-called suicide gene into microglia cells and the administration of pharmaceutical agents which led to a systematic death of the cells.
Surprisingly and against all predictions, the ablation of microglia had, however, no effect on the amount of amyloid deposits. The fact whether the microglia cells were eliminated before or after the formation of amyloid-beta protein deposits made no difference. From cell culture experiments it is known that, in principle, microglia cells do have the ability to reduce amyloid plaques. The reason why this effect does not occur in the brains of the mouse models will now be addressed in future studies. The answer to this question could pave the way to a new therapeutic approach for Alzheimer's disease.Title of the original publication:
Stefan A Grathwohl, Roland E Kälin, Tristan Bolmont, Stefan Prokop, Georg Winkelmann, Stephan A Kaeser, Jörg Odenthal, Rebecca Radde, Therese Eldh, Sam Gandy, Adriano Aguzzi, Matthias Staufenbiel8, Paul M Mathews, Hartwig Wolburg, Frank L Heppner, Mathias Jucker
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