Cystatins the crucial inhibitors for proper brain functioning have been reported from several mammalian sources and an imbalance of proteinases (cathepsins) with their endogenous inhibitor cystatins is closely associated with senile plaque, cerebrovascular amyloid deposits, and neurofibrillary tangles in Alzheimer's disease. Here, CST4 is linked to early-onset autosomal dominant Alzheimer disease.