In situ immunodetection of neuronal caspase-3 activation in Alzheimer disease

The mechanism by which cells die in Alzheimer disease (AD) is unknown. Seve ral investigators speculate that much of the cell loss may be due to apopto sis, a highly regulated form of programmed cell death. Caspase-3 is a criti cal effector of neuronal apoptosis and may be inappropriately activated in AD. To address this possibility, we examined cortical and hippocampal brain sections from AD patients, as well as 2 animal models of AD, for in situ e vidence of caspase-3 activation. We report here that senile plaques and neu rofibrillary tangles in the AD brain are not associated with caspase-3 acti vation. Furthermore, amyloid beta (AP) deposition in the APPsw transgenic m ouse model of ED does not result in caspase-3 activation despite the abilit y of AP to induce caspase-3 activation and neuronal apoptosis in vitro. AD brain sections do, however, exhibit caspase-3 activation in hippocampal neu rons undergoing granulovacuolar degeneration. Our data suggests that caspas e-3 does not have a significant role in the widespread neuronal cell death that occurs in AD, but may contribute to the specific loss of hippocampal n eurons involved in learning and memory.