A novel approach for characterization of cathepsin D protease and its effect on tau and β-amyloid proteins.

Cathepsin D is the lysosomal protease abundantly expressed in the brain. It plays an important role in the regulation of cellular apoptosis. In addition, cathepsin D has been shown to be involved in the pathogenesis of Alzheimer disease and autism. In this study, we developed a novel approach for the preparation of highly purified cathepsin D from the calf brain. This high grade purification is achieved by using DEAE-Sephacel Chromatography before the final step of applying to the Pepstatin-Sepharose 4B column. The properties of cathepsin D have also been studied. We show that cathepsin D cleaves both tau and β-amyloid precursor protein (APP). Both tau and APP are involved in the pathogenesis of Alzheimer's disease. Our findings strongly suggest a link between the lysosomal dysfunction of cathepsin D and the etiology of Alzheimer's disease. Our findings also indicate that cathepsin D could be a new approach to treating Alzheimer's disease.