It is reported recently that truncated tau at Glu391 and Asp421 presents in the patients of Alzheimer's disease (AD) brain, and caspase-3 is involved in tau truncation at Asp421. In vitro studies show that caspase-3 can cleaved tau only at Asp421 and the proteolytic cleavage of tau at Asp421 by caspase-3 generates a truncated tau fragment namely tau1-421, which enhances filament assembly in vitro. Expression of tau1-421 in neurons promotes apoptosis. It is not known that if phosphorylated tau is also a substrate of caspase-3. To understand the question, recombinant human tau protein was purified and phosphorylated with protein kinase A (PKA), calcium/calmodulin dependent protein kinase Ⅱ (CaMK Ⅱ ) or kinases from newborn rat hippocampi extract, and then these different tau species were cleaven by caspase-3. It was demonstrated that tau phosphorylated by PKA, CaMK Ⅱ and newborn hippocampi extract is also cleaven by caspase-3. As the phosphorylated tau also can be cleaven by caspase-3, it was speculated that phosphorylation tau is still the substrate of caspase-3.