Apoptosis is induced by beta-amyloid in cultured central nervous system neurons.

TLDR

Alzheimer’s disease neurodegeneration’s mechanism remains unclear, but accumulating evidence implicates beta‑amyloid peptides in driving neuronal loss. Synthetic beta‑amyloid peptides trigger apoptotic death in cultured neurons—manifested by membrane blebbing, chromatin condensation, and DNA fragmentation—which is attenuated by aurintricarboxylic acid, suggesting apoptosis contributes to Alzheimer’s neuronal loss.

Abstract

The molecular mechanism responsible for the neurodegeneration in Alzheimer disease is not known; however, accumulating evidence suggests that beta-amyloid peptide (A beta P) contributes to this degeneration. We now report that synthetic A beta Ps trigger the degeneration of cultured neurons through activation of an apoptotic pathway. Neurons treated with A beta Ps 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.