|Caspase Activation But Not Apoptosis
The article by Rissman and colleagues (2004) and accompanying commentary by Dickson (2004) highlight the potential importance of caspase activation in Alzheimer disease (AD). In the former, Rissmann et al. (2004) convincingly show that caspase-cleavage of tau, which may precede the phosphorylation of tau, serves to catalyze filament formation and thereby may be a key step in the development of the hallmark neurofibrillary pathology. However, there are several important caveats to consider here. While caspase activation may play a role in disease, this does not imply that apoptosis is also a feature of disease. Indeed, while there is demonstrable activation of initiator caspases in vulnerable neurons, this apparently does not lead to the cytoplasmic activation of executioner caspases, including the caspase 3 shown by Rissman to effect tau alterations (Raina et al., 2001). In fact, activation of caspase 3, where reported (Stadelmann et al., 1999), is restricted to granules of granulovacuolar degeneration.
Whether the phenomena...