Beta-amyloid induces local neurite degeneration in cultured hippocampal neurons: evidence for neuritic apoptosis

Many apoptotic insults, including beta-amyloid, cause neuritic degeneration. The possibility that apoptotic insults act directly on neurites was investigated in experiments using compartmented cultures of hippocampal neurons. Neurites in modified Campenot chambers displayed morphological signs of degeneration, including beading or blebbing, when exposed to beta-amyloid. At short time points neurite degeneration was limited to the distal portions of neurites directly exposed to beta-amyloid. Furthermore, annexin V binding detected extracellular exposure of phosphatidylserine in portions of neurites directly exposed to apoptotic insults. Pretreatment of the cultures with zVAD-fmk blocked annexin V binding induced by beta-amyloid and concanavalin A, suggesting that caspase activity was required. Caspase activation was also visualized in neurites locally exposed to apoptotic insults. Together these results show that apoptotic insults cause local neurite degeneration which displays morphological and biochemical characteristics of apoptosis and suggest that neurite degeneration may use mechanisms common to apoptosis.