PROTEOLYTIC PROCESSING OF AMYLOID BETA-PROTEIN PRECURSOR (APP) BY THROMBIN

Search for proteases responsible for an altered processing of APP which generates intermediates containing β A4 peptide is preceding to understand the formation of β amyloid deposits characteristic of Alzheimer's disease, since many studies reveal that APP is ordinarily processed so as not to generate β amyloid. Here, we have examined the action of thrombin, a serine protease in the blood clotting, in APP processing. Thrombin cleaved the mouse recombinant APP695in vitro, resulting in the accumulation of 28 kDa fragment. The immunoblot analysis showed that the fragment is derived from the carboxy-terminal side of the recombinant APP695. Further, amino acid sequencing exhibited that the fragment is generated by the cleavage at Arg 510 - lle 511 and therefore includes entire β A4 peptide. We consider that the 28 kDa fragment is a possible intermediate for β A4 peptide. Thus thrombin may be involved in the altered processing of APP. © 1992.