Neuropathological Staging of Spinocerebellar Ataxia Type 2 by Semiquantitative 1 C 2‐Positive Neuron Typing. Nuclear Translocation of Cytoplasmic 1 C 2 Underlies Disease Progression of Spinocerebellar Ataxia Type 2

Spinocerebellar ataxia type 2 ( SCA 2) is a hereditary neurodegenerative disorder caused by the expansion of the trinucleotide CAG repeats encoding elongated polyglutamine tract in ataxin‐2, the SCA 2 gene product. Polyglutamine diseases comprise nine genetic entities, including seven different forms of spinocerebellar ataxias, H untington's disease, and spinal and bulbar muscular atrophy. These are pathologically characterized by neuronal loss and intranuclear aggregates or inclusions of mutant proteins including expanded polyglutamine in selected neuronal groups. Previously, we examined immunolocalization of ubiquitin, expanded polyglutamine (probed by 1 C 2 antibody), and ataxin‐2 in genetically confirmed SCA 2 patients. In the present study, we expanded this approach by distinguishing different patterns of subcellular 1 C 2 immunoreactivity (“granular cytoplasmic,” “cytoplasmic and nuclear” and “nuclear with inclusions.”) and by quantifying their regional frequencies in three autopsied SCA 2 brains at different stage of the disease. Comparison with neuronal loss and gliosis revealed that overall 1 C 2 immunoreactivity was paralleled with their severity. Furthermore, appearance of granular cytoplasmic pattern corresponded to early stage, cytoplasmic and nuclear pattern to active stage, and nuclear with inclusions pattern to final stage. We conclude that this 1 C 2‐immunoreactive typing may be useful for evaluating the overall severity and extent of affected regions and estimating the neuropathological stage of SCA 2.