Amyloid β peptide induces necrosis rather than apoptosis

Abstract

Amyloid β peptide (AβP), a major component of Alzheimer's disease plaques, is toxic to rat pheochromocytoma PC12 cells and to rat cortical neurons. A reduction in cell survival could be detected after 24 h incubation with 0.01 to 20 μM of the 25–35 peptide fragment (β25–35) of AβP. To study the mechanism of cell death induced by AβP, the morphological as well as the biochemical features of neuronal cell death were analyzed. To distinguish between necrosis and apoptosis, PC12 cell death caused by β25–35 was compared to that induced by serum deprivation, a process known to be apoptotic in these cells. The DNA-degradation pattern of AβP treated cells appeared random rather than at distinct internucleosomal sites as with apoptosis. Electron microscopic studies of NGF-treated PC12 cells and cortical primary cultures exposed to 20 μM β25–35 revealed immediate cellular damage such as vacuolization of the cytoplasm, breakdown of Golgi-apparatus and other membrane systems, and neurite disintegration. This was followed by total collapse of the cytoplasm and cell lysis. These data show that AβP toxicity occurs via a necrotic rather than an apoptotic pathway.