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

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