Neuronal intranuclear inclusions in spinocerebellar ataxia type 2: triple-labeling immunofluorescent study

Spinocerebellar ataxia type 2 (SCA2) is associated with an expansion of CAG/polyglutamine-repeat of a gene of unknown function. We performed an immunohistochemical study to identify the immunolocalization of the disease protein ataxin-2 in normal and SCA2 patients. Although normal and expanded ataxin-2 were ubiquitously localized to the cytoplasm of neurons, ubiquitinated intranuclear inclusions were observed selectively in 1-2% of neurons of affected brain regions except the cerebellum. Triple-labeling immunofluorescence revealed that ataxin-2, expanded polyglutamine and ubiquitin were colocalized to these neuronal intranuclear inclusions (Nls), indicating that SCA2 shares morphological characteristics common to other neurological disorders associated with an expansion of CAG/polyglutamine-repeat. Lack of Nls in the cerebellar lesion, however, suggests the discrepancy between formation of Nls and neuronal degeneration in SCA2. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.