Manganese and copper-zinc superoxide dismutases in the human olfactory mucosa: Increased immunoreactivity in alzheimer's disease

Superoxide dismutases are the cell's major enzymatic defenses against cytotoxic reactive oxygen species and oxidative stress. Reactive oxygen species, which induce the expression of these enzymes, have been implicated in the neurodegeneration associated with Alzheimer's disease (AD), and individuals with AD exhibit early, severe deficits in olfactory ability. We used immunohistochemistry to examine the cellular localization of manganese and copper-zinc superoxide dismutases in the olfactory mucosae of nondemented young/middle-aged and old subjects as well as age- and postmortem-interval matched nondemented elderly individuals and those with AD. Tissues were obtained at autopsy from individuals ranging in age from 19 to 98 years old. Immunoreactivity for both enzymes was localized in olfactory receptor neurons, sustentacular and basal cells in the olfactory epithelium, and in olfactory and extrinsic nerves, Bowman's glands, and vascular endothelium in the lamina propria. Computer-assisted quantitative analysis demonstrated that very intense immunoreactivity for both manganese and copper-zinc superoxide dismutases occupied significantly more area, particularly near the surface and in the basal region, of the olfactory epithelium from subjects with AD than from the age- and postmortem interval matched nondemented elderly subjects. The pronounced increase in superoxide dismutase immunoreactivity in the olfactory epithelium of AD subjects suggests that oxidative stress may be responsible, at least in part, for the olfactory deficits in subjects with AD.