This study demonstrates elastase immunoreactivity in the neurofibrillary 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 protease for the generation of amyloid-β from β-protein precursor. These findings support the hypothesis that proteases play an important role in Alzheimer disease and furthers the notion that an imbalance in proteolytic regulation contributes towards the pathogenic presentation of the disease. Moreover, since α1-antitrypsin, the principal inhibitor of elastase, is highly susceptible to oxidative stress, our findings suggest a link between proteolytic imbalance and oxidative stress in the pathogenesis of Alzheimer disease.