SPINOCEREBELLAR ATAXIA TYPE-7 (SCA7) - A NEURODEGENERATIVE DISORDER WITH NEURONAL INTRANUCLEAR INCLUSIONS

Autosomal dominant cerebellar ataxia with progressive macular degenera tion is caused by a CAG/glutamine repeat expansion in the SCA7 gene/pr otein. Neuronal intranuclear inclusions were detected in the brain of an early onset SCA7 case with the 1C2 antibody directed against an exp anded polyglutamine domain. Nuclear inclusions were most frequent in t he inferior olivary complex, a site of severe neuronal loss in SCA7. T hey were also observed in other brain regions, including the cerebral cortex, not considered to be affected in the disease. Using confocal m icroscopy we showed that some inclusions were ubiquitinated, but to va rying degrees, ranging from <1% in the cerebral cortex to 60% in the i nferior olive. In addition, we also observed cytoplasmic staining usin g the 1C2 antibody, particularly in the supramarginal gyrus, the hippo campus, the thalamus, the lateral geniculate body and the pontine nucl ei. These data confirm that the presence of intranuclear inclusions in neurons is a common characteristic of disorders caused by CAG/polyglu tamine expansions, but unlike what has been reported for Huntington's disease, SCA1 and SCA3/MJD, in SCA7 the inclusions were not restricted to the sites of severe neuronal loss.