Tau cleavage is an early event modulated by caspase-3 activation in rTg4510 mice. Brain slices were analyzed from both control (white bars) and transgenic animals (black bars) at 2.5 months. Caspase-cleaved tau (truncated at Asp421) cells were identified by immunohistochemistry and the number of positive cells was counted in the olfactory bulb (OB), frontal cortex (FC), sensorimotor cortex (SMC), medial septal nucleus (MSN), subgranular zone (SGZ), subventricular zone (SVZ), CA1, and entorhinal cortex (EC). Total proteins of frontal cortex and hippocampus of both control and transgenic animals at 2.5, 5.5, and 8.5 months were extracted and analyzed by Western blot. A: Immunohistochemical staining in control FC (a); transgenic FC (b); control H (c); and transgenic H (d) (top) and number of caspase-cleaved tau positive cells (bottom). Positive cells were identified by dark staining. B: Representative immunoblots of caspase-cleaved tau. The results are expressed as mean ± SEM of at least three different experiments. *P < 0.01 and §P < 0.05 from control animals. The blots were normalized to total tau protein levels. Scale bar: 100 μm.