My research aims to understand the role of proteases in the pathogenesis of dege nerative diseases. Proteases play an important role in the cascade of events lea ding to cell death. Abnormal processing of proteins is an early event in several major degenerative disorders. We are particularly interested in characterizing the role of calpains (calcium-activated proteases) in Alzheimer's disease (AD) and Parkinson's disease (PD) and in understanding the interplay among the calpai n, caspase and cathepsin proteolytic systems in programmed cell death. I use bo th biochemical and immunochemical techniques to study proteases in postmortem hu man and animal tissues and in cell culture models. These studies also focus on t he regulation of endogenous inhibitors that modulate the activities of the prote ases. Based on our discovery of elevated lysosomal hydrolases in CSF of AD pati ents, we are developing a diagnostic test for Alzheimer's disease. I am current ly developing a sensitive assay for cathepsin D, a lysosomal enzyme especially e levated in AD brain and cerebrospinal fluid (CSF). The assay in conjunction with other available markers in CSF, such as tau protein and amyloid ( peptide, will yield a profile with increased detection sensitivity.