title: Neuropathological staging of spinocerebellar ataxia type 2 by semiquantitative 1C2-positive neuron typing. Nuclear translocation of cytoplasmic 1C2 underlies disease progression of spinocerebellar ataxia type 2.
abstract: Spinocerebellar ataxia type 2 (SCA2) is a hereditary neurodegenerative disorder caused by the expansion of the trinucleotide CAG repeats encoding elongated polyglutamine tract in ataxin-2, the SCA2 gene product. Polyglutamine diseases comprise nine genetic entities, including seven different forms of spinocerebellar ataxias, Huntington'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 1C2 antibody), and ataxin-2 in genetically confirmed SCA2 patients. In the present study, we expanded this approach by distinguishing different patterns of subcellular 1C2 immunoreactivity ("granular cytoplasmic," "cytoplasmic and nuclear" and "nuclear with inclusions.") and by quantifying their regional frequencies in three autopsied SCA2 brains at different stage of the disease. Comparison with neuronal loss and gliosis revealed that overall 1C2 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 1C2-immunoreactive typing may be useful for evaluating the overall severity and extent of affected regions and estimating the neuropathological stage of SCA2.
authors.affiliation: Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan; Laboratory of Structural Neuropathology, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Koyano
authors.forename: Saburo
authors.initials: S
authors.lastname: Yagishita
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kuroiwa
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.forename: Toshiki
authors.initials: T
authors.lastname: Uchihara
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000067528:Ataxins; D001284:Atrophy; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D002467:Cell Nucleus / Q000378:metabolism* / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005911:Gliosis / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D010455:Peptides / Q000378:metabolism; D020754:Spinocerebellar Ataxias / Q000473:pathology / Q000503:physiopathology*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D000067528:Ataxins; D009419:Nerve Tissue Proteins; D010455:Peptides; D025801:Ubiquitin; C097188:polyglutamine
keywords: 1C2-immunoreactive typing; cytoplasmic and nuclear; granular cytoplasmic; nuclear with inclusions; spinocerebellar ataxia type 2