HtrA2/Omi is a mitochondrial serine protease that promotes apoptotic processes, and this study investigated whether the abnormal immunoexpression of HtrA2/Omi occurs in patients with Alzheimer's disease. We prepared autopsied brains from seven control individuals and seven patients with Alzheimer's disease, and then carried out immunohistochemical studies on HtrA2/Omi using formalin-fixed, paraffin-embedded sections from all of these cases. In the cerebral cortex and hippocampus from the cases of Alzheimer's disease, densely accumulated HtrA2/Omi immunoreactivity was scattered, both intracellularly and extracellularly. Double immunofluorescence analyses showed the partial localization of HtrA2/Omi immunoreactivity in amyloid β-peptide-immunopositive senile plaques and phosphorylated τ-immunopositive neurofibrillary tangles. These results suggest that HtrA2/Omi may be partially associated with the pathogenesis of Alzheimer's disease.