Amyloid beta peptide induces necrosis rather than apoptosis

• Published in: Brain research Vol. 645; no. 1-2; p. 253
• Main Authors: Behl, C, Davis, J B, Klier, F G, Schubert, D
• Format: Journal Article
• Language: English
• Published: Netherlands 09-05-1994
• Subjects: Amyloid beta-Peptides - pharmacology; Animals; Apoptosis; Cell Death; DNA Damage; Flow Cytometry; Microscopy, Electron; Necrosis; Nerve Growth Factors - pharmacology; PC12 Cells - drug effects; PC12 Cells - pathology; PC12 Cells - ultrastructure; Rats
• ISSN: 0006-8993
• DOI: 10.1016/0006-8993(94)91659-4

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.