Abstract: The present invention relates to a novel animal model for amyloidopathies, especially Alzheimer' disease overexpressing human BACE and human APP London. This novel animal model exhibits several aspects of amyloidopathy. The present invention also relates to a method for producing the double transgenic animals, to cells and cell lines derived from these animals and to a kit comprising these cells. Moreover, a method for the evaluation of the in vivo effects of beta-secretase activity on A-beta peptide generation, amyloidosis, neurodegeneration and AD pathology in these animals is provided.

Abstract: Modified phosphodiesterase (PDE) polypeptides with altered physicochemical properties are disclosed, together with the polynucleotides encoding such modified PDE polypeptides, antibodies against such polypeptides and methods of preparation. Such polypeptides are useful for screening assays for identification of agonists or antagonists of phosphodiesterase activity.

Abstract: The present invention relates to a novel animal model for amyloidopathies, especially Alzheimer' disease overexpressing human BACE and human APP London. This novel animal model exhibits several aspects of amyloidopathy and has utility in developping specific and general therapies for amyloidopathies. Moreover, this animal model can be used for screening methods to identify novel anti-amyloidogenic compounds and for testing their therapeutic effect. The present invention also relates to a method for producing the said double transgenic animals, to cells and cell lines derived from these animals and to a kit comprising these cells for screening compounds useful of amyloidopathies. Moreover, a method for the evaluation of the in vivo effects of beta-secretase activity on A-beta peptide generation, amyloidosis, neurodegeneration and AD pathology in these animals is provided.

Abstract: The present invention relates to an assay for identifying inhibitors of beta-secretases comprising the steps of immobilizing a beta-secretase protein on a solid support, contacting it with a test compound in the presence of a tagged beta-secretase inhibitor, and comparing the extent of binding of the tagged beta-secretase inhibitor in the presence and in the absence of the test compound in order to evaluate if the test compound is an inhibitor of beta-secretases. The present invention also relates to a method of screening for inhibitors of beta-secretases, to novel beta-secretase inhibitors and their use as tagged beta-secretase inhibitors for identification of inhibitors of beta-secetase, to a kit for identifying beta-secretase inhibiotrs as well as to novel beta-secretase inhibitors for use in the treatment of Alzheimer's disease and other cerebrovascular amyloidosis.