A second cytotoxic proteolytic peptide derived from amyloid beta-protein precursor

The amyloid beta -protein precursor gives rise to the amyloid beta -protein , the principal constituent of senile plaques and a cytotoxic fragment invo lved in the pathogenesis of Alzheimer disease. Here we show that amyloid be ta -protein precursor was proteolytically cleaved by caspases in the C term inus to generate a second unrelated peptide, called C31. The resultant C31 peptide was a potent inducer of apoptosis. Both caspase-cleaved amyloid bet a -protein precursor and activated caspase-9 were present in brains of Alzh eimer disease patients but not in control brains. These findings indicate t he possibility that caspase cleavage of amyloid beta -protein precursor wit h the generation of C31 may be involved in the neuronal death associated wi th Alzheimer disease.