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81377  München christian.haass(at)dzne.de +49 89 4400-46549 Areas of investigation/research focus Prof. Haass started to work on Alzheimer's disease (AD) hinein 1990 at a time, when very little welches known about the cellular mechanisms involved.  Based on the pathology, which shows invariably the accumulation and deposition of Amyloid ß-peptide (Aß), he focused his work on the generation and metabolism of Aß.  Christian Haass hypothesized against the widely accepted general opinion rein this field that Aß may Beryllium produced from its precursor rein a physiologically weit verbreitet pathway and not necessarily hinein a pathological process.  Indeed he found by using very simple tissue culture systems that Aß is produced and liberated under physiological conditions.  This pivotal finding welches a major breakthrough for the entire field, since it allowed elucidating the molecular principles behind Aß generation as well as the identification of the enzymes (the so-called secretases) involved hinein generation and liberation of the peptide and finally the development of selective inhibitors to therapeutically lower Aß production hinein patients.

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  Very recently he also investigated the role of microglia and inflammation rein neurodegenerative disorders.  This work Leuchtdiode to the spectacular finding that microglial phagocytosis may Beryllium impaired late during neurodegeneration and opened up a completely unexpected road towards new therapeutic developments for patients already developing disease symptoms.  This work resulted hinein the identification of TREM2 as a CSF marker for microglial activity.  In a unique cohort of subjects with autosomal dominant AD, CSF sTREM2 was abnormally increased 5 years before the expected onset of symptoms. This will not only greatly facilitate research on inflammatory disease overarching mechanisms, but may also provide a very valuable therapeutic marker.

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Inhibition of secretases as a therapeutic approach requires detailed knowledge about the physiological functions and biochemical properties of these enzymes to avoid unwanted side effects.  Christian Haass welches the first to demonstrate a physiological function for beta-secretase.  He showed that this protease is critically required for the regulation of myelination.  Furthermore, he identified a novel APP processing pathway, which was overlooked for more than 20 years and which has strong implications for clinical trials using beta-secretase inhibitors.  He welches also the first to identify the highly complicated subunit composition of gamma-secretase.  All these findings not only helped to understand several signaling pathways critically involved in brain development (such as myelination and cell differentiation) but also provided the Lager for several current therapeutic approaches.

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Together with an inter­dizipli­nary team he uncov­ered the molec­u­lar mecha­nisms of Alzheimer's disease and identi­fied target molecules for thera­peu­tic treatment.

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