The neuropathology of a chromosome 17-linked autosomal dominant parkinsonism and dementia ('pallido-ponto-nigral degeneration')

L. A. Reed, M. L. Schmidt, Zbigniew K Wszolek, B. J. Balin, V. Soontornniyomkij, V. M Y Lee, J. Q. Trojanowski, R. L. Schelper

Research output: Contribution to journalArticle

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Abstract

A group of similar autosomal dominant hereditary neurodegenerative disorders have been linked to chromosome 17 in thirteen kindreds. One of these disorders, known as pallido-ponto-nigral degeneration (PPND), is characterized by extensive degeneration of the globus pallidus and substantia nigra as well as accumulation of abnormally phosphorylated tau proteins. The authors now present comprehensive data on the cellular and molecular pathology of PPND, allowing its classification among chromosome 17-linked neurodegenerative disorders as well as its classification among sporadic and other familial tauopathies. First, we showed that PPND is characterized by abundant ballooned neurons in neocortical and subcortical regions as well as by tau-rich inclusions in the cytoplasm of neurons and oligodendroglia morphologically similar to those seen in corticobasal degeneration (CBD), but in a distribution pattern resembling progressive supranuclear palsy (PSP). Second, we demonstrated that antibodies to phosphorylation-independent (Alz50, 133, 304, Tau-2, T-46) as well as phosphorylation-dependent (AT8, PHF-6, 12E8, PHF-1, T3P, pS422) epitopes in human tau proteins stain these glial and neuronal inclusions as intensely as they stain CBD or PSP inclusions. Third, we probed PPND brain by Western blots using some of the same anti-tau antibodies to reveal 2 tau immunobands with molecular weights of 69 kD and 64 kD in gray and white matter extracts, as reported for both PSP and CBD. Finally, electron microscopy showed that these abnormal tau proteins formed fiat twisted ribbons with a maximum diameter of 20 nanometers (nm) and a periodicity of about 200 nm, resembling those reported in CBD. Based on this, we conclude that PPND is a hereditary neurodegenerative disorder characterized by neuronal and glial tau-rich inclusions formed from aggregated filaments and hyperphosphorylated tau proteins and, hence, can be subcategorized into the tauopathy group of chromosome 17-linked neurodegenerative disorders. Further, since the morphologic and biochemical lesions of PPND overlap with those seen in sporadic CBD and PSP, we speculate that these disorders share common pathogenetic mechanisms.

Original languageEnglish (US)
Pages (from-to)588-601
Number of pages14
JournalJournal of Neuropathology and Experimental Neurology
Volume57
Issue number6
StatePublished - Jun 1998
Externally publishedYes

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Chromosomes, Human, Pair 17
Parkinsonian Disorders
Substantia Nigra
Dementia
Progressive Supranuclear Palsy
tau Proteins
Neurodegenerative Diseases
Tauopathies
Neuroglia
Coloring Agents
Phosphorylation
Neurons
Globus Pallidus
Molecular Pathology
Oligodendroglia
Periodicity
Neuropathology
Epitopes
Anti-Idiotypic Antibodies
Electron Microscopy

Keywords

  • Chromosome 17
  • Corticobasal degeneration
  • Frontotemporal dementia
  • Pallido- ponto-nigral-degeneration
  • Parkinsonism
  • Progressive supranuclear palsy
  • Tau proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

The neuropathology of a chromosome 17-linked autosomal dominant parkinsonism and dementia ('pallido-ponto-nigral degeneration'). / Reed, L. A.; Schmidt, M. L.; Wszolek, Zbigniew K; Balin, B. J.; Soontornniyomkij, V.; Lee, V. M Y; Trojanowski, J. Q.; Schelper, R. L.

In: Journal of Neuropathology and Experimental Neurology, Vol. 57, No. 6, 06.1998, p. 588-601.

Research output: Contribution to journalArticle

Reed, LA, Schmidt, ML, Wszolek, ZK, Balin, BJ, Soontornniyomkij, V, Lee, VMY, Trojanowski, JQ & Schelper, RL 1998, 'The neuropathology of a chromosome 17-linked autosomal dominant parkinsonism and dementia ('pallido-ponto-nigral degeneration')', Journal of Neuropathology and Experimental Neurology, vol. 57, no. 6, pp. 588-601.
Reed, L. A. ; Schmidt, M. L. ; Wszolek, Zbigniew K ; Balin, B. J. ; Soontornniyomkij, V. ; Lee, V. M Y ; Trojanowski, J. Q. ; Schelper, R. L. / The neuropathology of a chromosome 17-linked autosomal dominant parkinsonism and dementia ('pallido-ponto-nigral degeneration'). In: Journal of Neuropathology and Experimental Neurology. 1998 ; Vol. 57, No. 6. pp. 588-601.
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