Establishment Of The Transgenic Model Of Alzheimer's Disease And The Study Of Pathogenesis

Alzheimer's disease (AD) is a progressive neurodegenerative disease, one of the major CNS diseases that keep troubling and threatening human health. Its basic pathological symptom is the accumulation of β-amyloid deposit in the brain. The principal component of amyloid is Aβ, which derives from β-amyloid precuser protein (β-APP).The most abundance APP isoform consists of 695, 751 and 770 amino acids. The 751- and 770- residue forms contain a 56- amino acids protease inhibitor domain that is homologous to the Kunitz type of serine protease inhibitors. In brain the 695 isoform predominates.Contemporary research shows that the mutation and overproduction of APP is closely related to the developing of AD. The lack of an animal model of AD has remained an impediment to the etiopathological studies and the drug development efforts. Most of the non-transgenic model failed to reproduce some features of the disease, transgenic animals have been used for establishment the animal model of AD.The thesis paper consists two parts. Part one: Establishment of the transgenic model of AD; part two: the study of APP metablish and pathogenesis on the basis of transgenic animal model.In part one the construction of the transgene and test of the expression were carrying out. Through microjection, transgenic mice carrying the mutant APP gene were produced. We constructed the transgene containing the human APP cDNA 695 V717I driven by PDGF promoter which expressed specifically in nervous system. With two respecting molar ratio of 3:3:1 and 1:1:1, the promoter, APP cDNA were subcloned into the vector. The...