Huntington's Disease (HD): Degeneration of Select Nuclei, Widespread Occurrence of Neuronal Nuclear and Axonal Inclusions in the Brainstem

Udo Rueb*, Matthias Hentschel, Katharina Stratmann, Ewout Brunt, Helmut Heinsen, Kay Seidel, Mohamed Bouzrou, Georg Auburger, Henry Paulson, Jean-Paul Vonsattel, Herwig Lange, Horst-Werner Korf, Wilfred den Dunnen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

27 Citations (Scopus)

Abstract

Huntington's disease (HD) is a progressive polyglutamine disease that leads to a severe striatal and layer-specific neuronal loss in the cerebral neo-and allocortex. As some of the clinical symptoms (eg, oculomotor dysfunctions) suggested a degeneration of select brainstem nuclei, we performed a systematic investigation of the brainstem of eight clinically diagnosed and genetically confirmed HD patients. This post-mortem investigation revealed a consistent neuronal loss in the substantia nigra, pontine nuclei, reticulotegmental nucleus of the pons, superior and inferior olives, in the area of the excitatory burst neurons for horizontal saccades, raphe interpositus nucleus and vestibular nuclei. Immunoreactive intranuclear neuronal inclusions were present in all degenerated and apparently spared brainstem nuclei and immunoreactive axonal inclusions were observed in all brainstem fiber tracts of the HD patients. Degeneration of brainstem nuclei can account for a number of less well-understood clinical HD symptoms (ie, cerebellar, oculomotor and vestibular symptoms), while the formation of axonal aggregates may represent a crucial event in the cascades of pathological events leading to neurodegeneration in HD.

Original languageEnglish
Pages (from-to)247-260
Number of pages14
JournalBRAIN PATHOLOGY
Volume24
Issue number3
DOIs
Publication statusPublished - Apr-2014

Keywords

  • axonal inclusions
  • brainstem
  • Huntington's disease
  • neurodegeneration
  • pathoanatomy
  • polyglutamine diseases
  • UBIQUITIN-PROTEASOME SYSTEM
  • MACHADO-JOSEPH-DISEASE
  • NERVE-CELL LOSS
  • INTRANUCLEAR INCLUSIONS
  • SPINOCEREBELLAR ATAXIAS
  • FUNCTIONAL NEUROANATOMY
  • TRINUCLEOTIDE REPEAT
  • DYSTROPHIC NEURITES
  • PARKINSONS-DISEASE
  • TYPE-3 SCA3

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