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

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