Immunohistochemical localization of X-linked inhibitor of apoptosis protein in brainstem-type and cortical Lewy bodies.

Abstract

X-linked inhibitor of apoptosis protein (XIAP) blocks the apoptosis by binding to and inhibiting caspases-3, 7, and 9. XIAP is negatively regulated by the mitochondrial serine protease, HtrA2/Omi. The aim of this study was to investigate the role of XIAP and the relationship between XIAP and HtrA2/Omi in patients with Parkinson's disease or dementia with Lewy bodies. We conducted immunohistochemical studies on XIAP in formalin-fixed, paraffin-embedded sections from eight normal participants, 10 patients with Parkinson's disease, five patients with dementia with Lewy bodies, and seven patients with Alzheimer's disease, and then double-labeling immunohistochemistry for XIAP and HtrA2/Omi in sections from the Parkinson's disease and dementia with Lewy bodies cases. Brainstem-type and cortical Lewy bodies were intensely immunostained for XIAP, and XIAP immunoreactivity was localized to the halos of brainstem-type Lewy bodies and to the entire bodies of cortical Lewy bodies. Double immunofluorescence analyses showed that XIAP and HtrA2/Omi immunoreactivities were colocalized to both types of Lewy bodies. Our results suggest that XIAP may be partially associated with the pathogenesis of Parkinson's disease and dementia with Lewy bodies.