Spinocerebellar ataxia type 7 (SCA7): a neurodegenerative disorder with neuronal intranuclear inclusions

Autosomal dominant cerebellar ataxia with progressive macular degenerationis caused by a CAG/glutamine repeat expansion in the SCA7 gene/protein.Neuronal intranuclear inclusions were detected in the brain of an earlyonset SCA7 case with the 1C2 antibody directed against an expandedpolyglutamine domain. Nuclear inclusions were most frequent in the inferiorolivary complex, a site of severe neuronal loss in SCA7. They were alsoobserved in other brain regions, including the cerebral cortex, notconsidered to be affected in the disease. Using confocal microscopy weshowed that some inclusions were ubiquitinated, but to varying degrees,ranging from <1% in the cerebral cortex to 60% in the inferior olive. Inaddition, we also observed cytoplasmic staining using the 1C2 antibody,particularly in the supramarginal gyrus, the hippocampus, the thalamus, thelateral geniculate body and the pontine nuclei. These data confirm that thepresence of intranuclear inclusions in neurons is a common characteristicof disorders caused by CAG/polyglutamine expansions, but unlike what hasbeen reported for Huntington's disease, SCA1 and SCA3/MJD, in SCA7 theinclusions were not restricted to the sites of severe neuronal loss.