A large transmembrane glycoprotein, which has been shown to play a major role in the pathogenesis of Alzheimer’s disease, as well as other related cerebral amyloid diseases. APP is made of 695 amino acids (APP-695). In 1988, three research groups simultaneously reported the isolation of cDNA clones that were shown to contain one or two additional domains compared with original APP-695. One of them showed extensive similarity to the Kunitz family of serine protease inhibitors (KPI) and resulted in a 56 amino acid insertion within the extracellular domain of the precursor protein. Therefore, the APPgene transcript and the corresponding APPprotein that contain the nucleotide sequence or amino acid sequence, respectively, encoding this insert are denoted as KPI-APP or APP-751. APP-695 is predominantly expressed in the brain during development. The level of KPI-APP or APP-751 increased during ageing.
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