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In a study published in Nature Neuroscience Stefan Grathwohl and the team of Mathias Jucker (Hertie-Institute for Clinical Brain Research, University of Tübingen) managed, in collaboration with the team of Frank Heppner (Department of Neuropathology, Charité-Universitätsmedizin Berlin), to develop a new transgenic mouse model of Alzheimer's disease, in whith, microglia cells can be nearly completely ablated. This was prerequisite to go one step further: The scientists analyzed what effect the ablation of microglia cells had on amyloid deposits in the mouse brains. The surprising result: Microglia cells are neither involved in the formation nor in the clearance of amyloid deposits.
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:
Formation and maintenance of beta-amyloid plaques in Alzheimer's disease in the absence of microglia
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
Nature Neuroscience, in press 2009.
http://dx.doi.org/10.1038/nn.2432
Contact
Universitätsklinikum Tübingen
Zentrum für Neurologie
Hertie-Institut für klinische Hirnforschung (HIH)
Professor Mathias Jucker
Telefon: 07071-29-8 68 63
Mail: mathias.jucker@uni-tuebingen.de
http://www-hih-tuebingen.de
Kirstin Ahrens
Pressereferentin Hertie-Institut für klinische Hirnforschung (HIH)
Telefon: 07073-500 724
Mobil: 0173-300 53 96
kirstin.ahrens@t-online.de
Criteria of this press release:
Medicine
transregional, national
Research results, Scientific Publications
English
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