Neuronal dysfunctions in several neurodegenerative diseases such as Down syndrome (DS) have been linked to oxidative stress. In this study, we observed that lipid peroxidation, a marker of oxidative stress, is significantly increased in the frontal cortex of brains of individuals with DS as compared with control subjects. We report here that gelsolin levels are increased in the frontal cortex of individuals with DS as compared with controls during early developmental ages (5 to 13 y). Interestingly, the levels of gelsolin in the frontal cortex were increased as a function of age in both DS and control subjects. Because cytoplasmic gelsolin has 5 free thiol groups (cysteine), and its levels are increased in response to oxidative stress, we propose that gelsolin may serve as an antioxidant protein.