摘要:
The construction of transgenic animal models of human Alzheimer's disease, and methods of using the models to screen potential Alzhe## disease therapeutics, are described. The models are characterized by pathologies similar to pathologies observed in Alzheimer's disease, based on expression of all three forms of the β-amyloid precursor protein (APP), APP695, APP751, and APP770, as well as various point mutations based on naturally occurring mutations, such as the London and Indiana familial Alzheimer's disease (FAD) mutations at amino acid 717, predicted mutations in the APP gene, and truncated forms of APP that contain the Aβ region. Animal cells can be isolated from the transgenic animals or prepared using the same constructs with standard techniques such as lipofection or electroporation. The transgenic animals, or animal cells, are used to screen for compounds altering the pathological course of Alzheimer's disease as measured by their effect on the amount of APP, β-amyloid peptide, and numerous other Alzheimer's disease markers in the animals, the neuropathology of the animals, as well as by behavioral alterations in the animals.
摘要:
Processing of .beta.-amyloid precursor protein (.beta.APP) is monitored by detecting the secretion of a soluble amino-terminal fragment or .beta.APP (ATF-.beta.APP) resulting from cleavage of .beta.APP at the amino-terminus of .beta.-amyloid peptide. Secretion of ATF-.beta.APP in animal models may be monitored to identify inhibitors of .beta.-amyloid production. The ATF-.beta.APP may be detected using antibodies and other specific binding substances which recognize a carboxy terminal residue on the fragment. Animals expressing the Swedish mutation of .beta.APP are described which produce abundant amounts of ATF-.beta.APP.
摘要:
The invention provides transgenic non-human animals and transgenic non-human mammalian cells harboring a transgene encoding an APP polypeptide comprising the Swedish mutation.
摘要:
The invention provides transgenic non-human animals and transgenic non-human mammalian cells harboring a transgene encoding an APP polypeptide comprising the Swedish mutation.
摘要:
The invention provides transgenic non-human animals and transgenic non-human mammalian cells harboring a transgene encoding an APP polypeptide comprising the Swedish mutation.
摘要:
The invention includes identification of specific markers, the elevation of which in central nervous tissue is associated with Alzheimer's Disease. The invention also includes improved assay methods for selecting compounds useful in reducing or preventing onset of the pathology associated with Alzheimer's Disease.