Abstract Extracellular neuritic plaques are a hallmark of Alzheimer's disease. The core protein of plaques is Aβ, a 39–43 amino acid peptide derived from the amyloid precursor protein (APP). APP C-100 is a C-terminal fragment of APP, 100 amino acids long, whose sequence includes Aβ. To determine whether APP C-100 expression alters cellular vulnerability to calcium and H 2O 2, rat PC12 cells were modified to overexpress APP C-100. Cellular survival (as measured in the MTT assay) was determined as a function of concentration for the calcium ionophore, A23187, and for H 2O 2 in APP C-100 transfectants and vector-transfected controls. APP C-100 expression significantly increased cellular vulnerability to A23187, and decreased vulnerability to H 2O 2.