The inherited neurodegenerative disorders such as the spinocerebellar ataxias, Huntington's disease, dentatorubral-pallidoluysian atrophy, and spinal and bulbar muscular atrophy associated with CAG/polyglutamine repeat expansion have been reported to exhibit intranuclear inclusions (NIs) in neurons. 1 In Annals, Huynh and colleagues 2 have reported the regional distribution of the spinocerebellar ataxia type 2 (SCA2) gene product, ataxin-2, in SCA2 brains. Although they identified ataxin-2-like immunoreactivity in the cytoplasm of neurons, NIs were reported to be absent in the cerebellum of SCA2 brains in their study.
We performed an immunohistochemical study to identify the immunolocalization of ataxin-2 in the cerebellum and other brain regions of autopsy brains from 3 Japanese patients genetically confirmed as having SCA2. We used antibodies against ataxin-2 (a well-characterized monoclonal antibody), 3 expanded polyglutamine (mAb 1C2), 4 and ubiquitin. Formalin-fixed, paraffin-embedded sections were stained by a standard immunohistochemical technique after pretreatment with periodic acid and microwave oven. This ataxin-2-like immunoreactivity was mainly in the cytoplasm and, to a lesser extent, in the nuclei of neurons, and NIs were not found in Purkinje cells in any of these three SCA2 cases, as reported by Huynh and colleagues. 2 In addition, we identified a round intranuclear structure immunolabeled by three antibodies (Fig) outside the cerebellum. They were usually solitary, distinguishable from the nucleolus and 1 to 5 mm in diameter. Because they were not found in nonneuronal cells or in normal brains, they were assumed to correspond to NIs. In all these three SCA2 brains, NIs were found most frequently in the ventral region of the pons, and 1% to 2% of the remaining pontine neurons contained NIs. They appeared in affected (the pontine nuclei, substantia nigra, and inferior olivary nucleus) but not in unaffected regions (the dentate nucleus and cranial nerve nuclei). Identification of NIs in SCA2 brains indicates that SCA2 may, at least partly, share pathogenic mechanisms common to other CAG/polyglutamine repeat disorders with NIs.