Spinocerebellar ataxia type 6 (SCA6): neurodegeneration goes beyond the known brain predilection sites

K. Gierga, H. J. Schelhaas, E. R. Brunt, K. Seidel, W. Scherzed, R. Egensperger, R. A. I. de Vos, W. den Dunnen, P. F. Ippel, E. Petrasch-Parwez, T. Deller, L. Schoels, U. Rueb*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    32 Citations (Scopus)

    Abstract

    Aims: Spinocerebellar ataxia type 6 (SCA6) is a late onset autosomal dominantly inherited ataxic disorder, which belongs to the group of CAG repeat, or polyglutamine, diseases. Although, it has long been regarded as a 'pure' cerebellar disease, recent clinical studies have demonstrated disease signs challenging the view that neurodegeneration in SCA6 is confined to the well-known lesions in the cerebellum and inferior olive. Methods: We performed a systematic pathoanatomical study throughout the brains of three clinically diagnosed and genetically confirmed SCA6 patients. Results: This study confirmed that brain damage in SCA6 goes beyond the known brain predilection sites. In all of the SCA6 patients studied loss of cerebellar Purkinje cells and absence of morphologically intact layer V giant Betz pyramidal cells in the primary motor cortex, as well as widespread degeneration of brainstem nuclei was present. Additional damage to the deep cerebellar nuclei was observed in two of three SCA6 patients. Conclusions: In view of the known functional role of affected central nervous grey components it is likely that their degeneration at least in part is responsible for the occurrence of a variety of SCA6 disease symptoms.

    Original languageEnglish
    Pages (from-to)515-527
    Number of pages13
    JournalNeuropathology and Applied Neurobiology
    Volume35
    Issue number5
    DOIs
    Publication statusPublished - Oct-2009

    Keywords

    • channelopathies
    • pathoanatomy
    • polyglutamine diseases
    • spinocerebellar ataxia type 6
    • spinocerebellar ataxias
    • ALPHA(1A)-VOLTAGE-DEPENDENT CALCIUM-CHANNEL
    • CENTRAL SOMATOSENSORY SYSTEM
    • CONSISTENT AFFECTION
    • PRECEREBELLAR NUCLEI
    • MOLECULAR-FEATURES
    • STEM NUCLEI
    • CAG-REPEAT
    • DEGENERATION
    • INVOLVEMENT
    • SECTIONS

    Cite this