| 摘要 |
The construction of transgenic animal models for testing potential treatments for Alzheimer's disease are described. The models are characterized by pathology similar to that observed in Alzheimer's disease, based on expression of all three forms of the beta -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 A beta region. The APP gene constructs are prepared using the human platelet derived growth factor B(PDGF-B) chain gene promoter, or other promoters able to express A DOLLAR (b) or mutant forms APP at a high level in transgenic animal brain tissue. 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 and beta -amyloid peptide, neuropathology, and behavioral alterations. |
