The tau protein is a microtubule-associated protein mainly expressed in neurons, which plays a crucial role in the neuronal cytoskeleton stabilization. The main role of tau proteins is to stabilize microtubules.Tau proteins are abundant in neurons of the central nervous system and are less common elsewhere, but are also expressed at very low levels in astrocytes and oligodendrocytes. Defects in tau proteins can result in dementias, such as Alzheimer's disease (AD). AD is a neurodegenerative pathology which is characterized by the presence of two types of neuropathological hallmarks: neurofibrillary tangles (NFTs) and senile plaques. NFTs are intraneuronal aggregations mainly composed of abnormally phosphorylated Tau. In neuropil threads (NPTs), NFTs, and neuritic plaques (NPs) of severe AD brains, highly abundant amounts of active caspase-6 and tau cleaved by caspase-6 (TauΔCsp6) have been found. 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. Caspase-6 has been associated with increasing β-amyloid peptide in primary cultures of human neurons. Caspase-6 has also been demonstrated to be active in NPTs, NFTs, and NPs in the hippocampus and temporal cortex in sporadic AD. Caspase-6 activation has been suggested to be an early event in AD and to precede the development of lesions.