EVIDENCE FOR OXIDATIVE STRESS IN PICK DISEASE AND CORTICOBASAL DEGENERATION

Oxidative stress is increasingly implicated in a number of neurodegene rative disorders characterized by abnormal filament accumulation in af fected neurons, including Alzheimer disease, Parkinson disease, and am yotrophic lateral sclerosis. To further evaluate the role of oxidative stress in the neurodegenerative process and the accumulation of abnor mal filaments, we examined the pathologic lesions in Pick disease and of corticobasal degeneration with immunocytochemistry by using antiser a to heme oxygenase-1 (HO-1) - a putative marker of oxidative injury. Immunoreactivity to HO-1 was demonstrated in ballooned neurons, Pick b odies, neuropil threads, and glial inclusions (the latter two in a cas e of corticobasal degeneration). By immunoelectron microscopy, HO-1 im munolabelling of Pick bodies was closely associated with the abnormal filaments comprising the inclusion. Apparently unaffected neurons in a ll cases showed only background levels of HO-1 immunoreactivity. These data suggest that oxidative stress is important in the formation of t he lesions characteristic of Pick disease and corticobasal degeneratio n. Moreover, taken together with our previous demonstration that HO-1 immunoreactivity is associated with the neurofibrillary pathology of A lzheimer disease, progressive supranuclear palsy, and subacute scleros ing panencephalitis, it appears that oxidative stress specifically tar gets the cytoskeleton in a variety of neurodegenerative disorders char acterized by abnormal filament accumulation.