Accumulation of a 50 kDa N-terminal fragment of beta-APP695 in Alzheimer's disease hippocampus and neocortex

Abstract

Proteolytic processing of beta-amyloid precursor protein (beta-APP) is a key event in the formation of beta-amyloid deposits in Alzheimer's disease (AD) brains and is likely to be accompanied by the accumulation of cleavage products other than the beta/A4 protein. Using a beta-APP695-specific monoclonal antibody in quantitative immunoblotting, a 50 kDa N-terminal fragment of beta-APP695 was detected in neocortex, hippocampus and cerebellum of AD patients and control individuals. The mean level of this fragment was higher in AD hippocampus and neocortex as compared to controls, suggesting that beta-APP695 fragments are generated in various brain regions but that the proteolytic processing is increased in pathologically affected brain areas.