ABERRANT TAU-PHOSPHORYLATION AND NEURITE RETRACTION DURING NGF DEPRIVATION IN PC12 CELLS

Recently apoptotic markers have been found in Alzheimer's Disease (AD) brain. To investigate the relation between tau phosphorylation and ap optosis, immunocytochemistry of AT8 (indicating the degree of phosphor ylation at the tau Ser202/Thr205 site) was quantitatively determined t he degree of tau phosphorylation at the Ser202 site was monitored duri ng neuronal apoptosis in differentiated PC12 cells after nerve growth factor (NGF) deprivation. During this programmed cell death a prominen t retraction of neurites took place that was associated with a clear i ncrease in the level of AT8 signalaberrant phosphorylated tau at the S er202 site. The broad spectrum kinase inhibitor staurosporine attenuat ed both this increase in tau phosphorylation, neurite retraction, and apoptosis. We suggest that at some point during programmed cell death, kinases with tau as substrate become activated and that the resulting loss of cytoskeletal integrity leads to neurite instability. (C) 1997 Academic Press.