Cathepsins that are typically localized in lysosomes, endosomes, or vesicles could be released into the cytoplasm of degenerating neurons (Roberg and Ollinger 1998) and generate an imbalance between cystatin C (inhibitor of proteases) and cathepsins (cysteine proteases), which has been associated to Alzheimer’s disease (Nakamura et al. 1991). Here, CST3 is linked to early-onset autosomal dominant Alzheimer disease.