I ncreasing evidence suggests that selective neuronal loss in neurodegenerative diseases involves activation of cysteine aspartyl proteases (caspases), which initiate and execute apoptosis. In Alzheimer disease both extracellular amyloid deposits and intracellular amyloid β protein may activate caspases, leading to cleavage of nuclear and cytoskeletal proteins, including tau protein. Proteolysis of tau may be critical to neurofibrillary degeneration, which correlates with dementia.