ELASTASE IS ASSOCIATED WITH THE NEUROFIBRILLARY PATHOLOGY OF ALZHEIMER-DISEASE - A PUTATIVE LINK BETWEEN PROTEOLYTIC IMBALANCE AND OXIDATIVE STRESS

This study demonstrates elastase immunoreactivity in the neurofibrilla ry pathology of Alzheimer disease. Using an antiserum against elastase , we show that elastase immunoreactivity is restricted to neurons and is markedly elevated in a proportion of neurofibrillary tangle-bearing neurons. Elastase is a proteolytic enzyme that might be a candidate p rotease for the generation of amyloid-beta from beta-protein precursor . These findings support the hypothesis that proteases play an importa nt role in Alzheimer disease and furthers the notion that an imbalance in proteolytic regulation contributes towards the pathogenic presenta tion of the disease. Moreover, since alpha(1)-antitrypsin, the princip al inhibitor of elastase, is highly susceptible to oxidative stress, o ur findings suggest a link between proteolytic imbalance and oxidative stress in the pathogenesis of Alzheimer disease.