title: Amyloid beta peptide induces necrosis rather than apoptosis.
abstract: Amyloid beta peptide (A beta P), 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 microM of the 25-35 peptide fragment (beta 25-35) of A beta P. To study the mechanism of cell death induced by A beta P, 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 beta 25-35 was compared to that induced by serum deprivation, a process known to be apoptotic in these cells. The DNA-degradation pattern of A beta P 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 microM beta 25-35 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 A beta P toxicity occurs via a necrotic rather than an apoptotic pathway.
authors.affiliation: Salk Institute for Biological Studies, San Diego, CA 92186-5800.
authors.forename: C
authors.initials: C
authors.lastname: Behl
authors.forename: J B
authors.initials: JB
authors.lastname: Davis
authors.forename: F G
authors.initials: FG
authors.lastname: Klier
authors.forename: D
authors.initials: D
authors.lastname: Schubert
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D016923:Cell Death; D004249:DNA Damage; D005434:Flow Cytometry; D008854:Microscopy, Electron; D009336:Necrosis; D009414:Nerve Growth Factors / Q000494:pharmacology; D016716:PC12 Cells / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D009414:Nerve Growth Factors