beta-APP processing and regulation by interleukin-1 in brain endothelial cells

Brain endothelial cells (BEC) cultured from brain autopsy samples from pati ents with Alzheimer's disease or from bovine brain produce a very similar p attern of beta-amyloid precursor protein (beta APP) synthesis and processin g. beta APP is processed mainly to non-amyloidogenic C-terminal fragments a nd to a secreted large N-terminal peptide corresponding to protease nexin I I. Interleukin 1 alpha treatment significantly increased the production of beta APP and the secretion of a large N-terminal fragment in these endothel ial cells. Additionally human BEC secrete proteases which can cleave beta A PP on the surface of thrombin stimulated platelets. Secretion of this appar ent proteolytic activity is not seen after exposure of the BEC to interleuk in 1 alpha (IL-1 alpha).