NMDA induces apoptosis and necrosis in neuronal cultures. Increased APP immunoreactivity is linked to apoptotic cells.

In rat neuronal cultures exposed for a prolonged period (16 h) to a low concentration of N-methyl-D-aspartate (NMDA; 20 microM) two different types of neuronal death were observed, necrosis and apoptosis. The immunocytochemical study of necrotic neurons revealed the absence of amyloid precursor protein (APP) labeling in the cytoplasmic region. In contrast, neuronal apoptosis was associated with an increase in cytoplasmic APP immunoreactivity. In addition, the presence of extracellular APP was also detected around some apoptotic neurons, suggesting that apoptosis could contribute to the presence of extracellular APP.