PC12 cells transfected with a C-terminal fragment of the amyloid precursor protein (APP C-100), exhibit enhanced sensitivity to the calcium ionophore A23187, and diminished sensitivity to hydrogen peroxide.
Extracellular neuritic plaques are a hallmark of Alzheimer's disease. The core protein of plaques is Abeta, 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 Abeta. To determine whether APP C-100 expression alters cellular vulnerability to calcium and H(2)O(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(2)O(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(2)O(2).