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

Nat Med. 2000 Apr;6(4):397-404. doi: 10.1038/74656.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Protein Precursor / genetics
  • Amyloid beta-Protein Precursor / metabolism*
  • Animals
  • Apoptosis
  • Brain / enzymology
  • Brain / pathology
  • Caspase 9
  • Caspases / genetics
  • Caspases / metabolism*
  • Cell Line, Transformed
  • Enzyme Activation
  • Humans
  • Mice
  • Peptide Fragments / metabolism
  • Peptides / metabolism*
  • Peptides / physiology
  • Substrate Specificity


  • Amyloid beta-Protein Precursor
  • Peptide Fragments
  • Peptides
  • amyloid precursor protein, carboxy-terminal 100 residues
  • CASP9 protein, human
  • Casp9 protein, mouse
  • Caspase 9
  • Caspases