Amyloid beta protein (A beta) is deposited characteristically in the brain of patients with Alzheimer's disease. Effects of protein kinase inhibitors (H-89, H-7, KN-62) on A beta-induced neuronal cell death were examined in primary culture of dissociated cerebral cortical cells. beta(25-35), the active fragment of A beta, induced neuronal cell death with apoptotic features including chromatin condensation and DNA fragmentation. The cell death was attenuated by cycloheximide or by H-89, a specific protein kinase A (PKA) inhibitor, but not by H-7 or KN-62. These data suggest that beta(25-35) induces apoptotic cell death through the PKA-mediated pathway.