BACKGROUND: Manganese-dependent superoxide dismutase (MnSOD) is a major defense mechanism against potential cellular damage by reactive oxygen species (ROS). We have reported increased lipid peroxidation and decreased Cu/Zn SOD enzymatic activity in the temporal cortex of Alzheimer's diseased (AD) brains. MATERIAL/METHODS: We now report the expression of MnSOD in the hippocampus of AD (n=8) and non-AD patients (n=7) via immunohistochemical methods, in both neuronal and non neuronal cells. We tested the hypothesis that there is differential expression of MnSOD in the CA1, CA2/3, and CA4 region of the hippocampus which may account for the neuronal loss seen in Alzheimer's disease. For neuronal cells, profile counts were made and expressed as positive neuronal profiles (MnSOD-IR) per mm(2) within hippocampal regions CA1, CA2/3, and CA4. RESULTS: The AD MnSOD-IR counts were over 9-fold higher in the CA2/3 region (p<0.001) and over 11-fold higher in the CA4 (p<0.001) region when compared to non-AD samples. The CA1 region in the AD samples showed the smallest increase (3-fold; p<0.05) when compared to non-AD patients. CONCLUSIONS: Since the CA1 region in AD is the most severely affected by the disease, our results suggest that normal compensatory mechanisms may be insufficient to protect this region from free radical oxidative damage.