Alzheimer's Disease  (Project 2)

Leader:   Prof. Dr. Roger Nitsch

A salient hallmark of Alzheimer’s disease is the deposition of senile plaques, which consist of beta-amyloid, in the brain. Therapies removing these plaques currently belong to the most promising strategies for the treatment and prevention of this severe disease. Although several immunotherapies, including antibody-based approaches developed in this project, are about to move into clinical trials, many mechanistic and structural aspects of the toxicity of the plaques remain unclear.

In this phase (2009 - 2013), we will thus investigate the biophysical mechanisms of Abeta aggregation which result in beta-amyloid plaques. We will also illuminate the role of the immune system in protecting against these toxic aggregates and characterize the pharmacological mechanisms of beta-amyloid-removal immunotherapies. The project will be strengthened significantly by a new assistant professorship. This will apply functional genomic, proteomic and computational tools to identify genes involved in the regulation of APP (beta-amyloid precursor protein) processing, which in turn can lead to beta-amyloid plaques in Alzheimer’s disease.

Confocal microscopy image of the immunostained hippocampus of ArcAbeta transgenic mice. The DIC image (left) shows the soma layer of CA1 pyramidal cells, apical dendrites pointing downwards. The expressed human amyloid precursor protein is labeled in green and the aggregated Abeta oligomers are seen as a red staining in vesicular structures. Scale bar 30 micrometer.

Publications of Project 2