APOPTOSIS IS INDUCED BY BETA-AMYLOID IN CULTURED CENTRAL-NERVOUS-SYSTEM NEURONS

The molecular mechanism responsible for the neurodegeneration in Alzheimer disease is not known; however, accumulating evidence suggests that beta-amyloid peptide (AbetaP) contributes to this degeneration. We now report that synthetic AbetaPs trigger the degeneration of cultured neurons through activation of an apoptotic pathway. Neurons treated with AbetaPs exhibit morphological and biochemical characteristics of apoptosis, including membrane blebbing, compaction of nuclear chromatin, and internucleosomal DNA fragmentation. Aurintricarboxylic acid, an inhibitor of nucleases, prevents DNA fragmentation and delays cell death. Our in vitro results suggest that apoptosis may play a role in the neuronal loss associated with Alzheimer disease.