Caspases are a family of cytosolic aspartate-specific cysteine proteases. Sequential activation of caspases plays a central role in the execution phase of cell apoptosis. Caspases exist as inactive proenzymes in the cytoplasm and are activated by dimerization or proteolytic cleavage. Together with caspase- 3, caspase- 6 is one of the major caspases in apoptotic cells, and functions downstream of apoptosis inhibitors Bcl-2 and Bcl-xL. Caspase- 6 has also been shown to be involved in the proteolysis of poly (ADP-ribose) polymerase (PARP) and nuclear lamin A. Recently, caspases have been considered to play roles in the neuronal cell death associated with Alzheimer’s disease (AD). Caspase-dependent increased β-amyloid peptide production can occur in various cell types; specifically, caspase- 6 is thought to be responsible for increasing β-amyloid peptide in primary cultures of human neurons. Caspase- 6 has also been demonstrated to be active in neuropil threads (NPTs), neurofibrillary tangles (NFTs), and neuritic plaques (NPs) in the hippocampus and temporal cortex in sporadic AD. A role for caspase- 6 in the regulation of axonal pruning of sensory and retinocollicular axons and axonal degeneration in sensory and motor mouse neurons has also been demonstrated. As a result of its involvement in the cleavage of important synaptic and cytoskeleton proteins, in the generation of high levels of β-amyloid peptide, and for being activated very early in cognitive impairment and Alzheimer’s disease (AD), activation of caspase- 6 has been considered to be involved in the development of AD.