A qualitative and quantitative study of grumose degeneration in progressive supranuclear palsy

Keisuke Ishizawa, Wen Lang Lin, Paul Tiseo, William G. Honer, Peter Davies, Dennis W. Dickson

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Grumose degeneration (GD) of the dentate nucleus is a common feature in progressive supranuclear palsy (PSP), but its pathogenesis has not been well studied, and its clinical significance remains unknown. This report describes a quantitative study of GD in 9 cases of PSP using image analysis with single- and double-immunolabeling, as well as histochemical stains for myelin and axons. GD was associated with demyelination, axonal loss, glial tau pathology, and microgliosis in regions juxtaposed to the dentate nucleus (DN). Specifically, demyelination and microgliosis were prominent in the superior cerebellar peduncle (SCP), dentate hilus, and cerebellar hemispheric white matter. Tau pathology and microgliosis were less prominent in the DN itself. The degree of myelin loss correlated with the tau burden in the SCP. GAP-43, which is a phosphoprotein known to be involved in axonal growth and sprouting, was decreased in the DN of PSP, and the degree of GAP-43 loss correlated with severity of GD. These results suggest that GD may be related to progressive pathology in the dentatorubrothalamic tract as well as the cerebellar hemispheric white matter, and that GD may be a consequence of concurrent degeneration in both output from and input to the DN. The results further suggest a possible role for oligodendroglial and myelin pathology in the pathogenesis of PSP.

Original languageEnglish (US)
Pages (from-to)513-524
Number of pages12
JournalJournal of Neuropathology and Experimental Neurology
Volume59
Issue number6
DOIs
StatePublished - Jun 2000

Keywords

  • Dentate nucleus
  • Grumose degeneration
  • Microglia
  • Oligodendroglia
  • Progressive supranuclear palsy
  • Tau

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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