EVIDENCE FOR OXIDATIVE STRESS IN PICK DISEASE AND CORTICOBASAL DEGENERATION

Oxidative stress is increasingly implicated in a number of neurodegenerative disorders characterized by abnormal filament accumulation in affected neurons, including Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. To further evaluate the role of oxidative stress in the neurodegenerative process and the accumulation of abnormal filaments, we examined the pathologic lesions in Pick disease and of corticobasal degeneration with immunocytochemistry by using antisera to heme oxygenase-1 (HO-1) - a putative marker of oxidative injury. Immunoreactivity to HO-1 was demonstrated in ballooned neurons, Pick bodies, neuropil threads, and glial inclusions (the latter two in a case of corticobasal degeneration). By immunoelectron microscopy, HO-1 immunolabelling of Pick bodies was closely associated with the abnormal filaments comprising the inclusion. Apparently unaffected neurons in all cases showed only background levels of HO-1 immunoreactivity. These data suggest that oxidative stress is important in the formation of the lesions characteristic of Pick disease and corticobasal degeneration. Moreover, taken together with our previous demonstration that HO-1 immunoreactivity is associated with the neurofibrillary pathology of Alzheimer disease, progressive supranuclear palsy, and subacute sclerosing panencephalitis, it appears that oxidative stress specifically targets the cytoskeleton in a variety of neurodegenerative disorders characterized by abnormal filament accumulation.