Caspase-mediated truncation of tau potentiates aggregation

Caspase-mediated truncation of tau is associated with aggregation. We examined the impact of manipulation of caspase activity on intracellular aggregation of a mutant form of tau (3PO) that forms spontaneous aggregates. Treatment with the caspase inhibitor Z-VAD-fmk reduced both N and C-terminal tau truncation but did not significantly reduce aggregation. Treatment with staurosporine, which activated caspases, increased C-terminal but not N-terminal truncation and enhanced aggregation. These findings suggest that caspase activation is one potential route, rather than an obligatory initiation step, in aggregation, and that N- and C-terminal truncation contribute differentially to aggregation.