Rapidly progressive dementia with thalamic degeneration and peculiar cortical prion protein immunoreactivity, but absence of proteinase K resistant PrP: a new disease entity?

Gabor G. Kovacs, Alexander Peden, Serge Weis, Romana Höftberger, Anna S. Berghoff, Helen Yull, Thomas Ströbel, Stefan Koppi, Regina Katzenschlager, Dieter Langenscheidt, Hamid Assar, Elisabeth Zaruba, Albrecht Gröner, Till Voigtländer, Gina Puska, Eva Hametner, Astrid Grams, Armin Muigg, Michael Knoflach, L. LászlóJames W. Ironside, Mark W. Head, Herbert Budka

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Abstract

BACKGROUND: Human prion diseases are a group of rare fatal neurodegenerative conditions with well-developed clinical and neuropathological diagnostic criteria. Recent observations have expanded the spectrum of prion diseases beyond the classically recognized forms.

RESULTS: In the present study we report six patients with a novel, apparently sporadic disease characterised by thalamic degeneration and rapidly progressive dementia (duration of illness 2-12 months; age at death: 55-81 years). Light and electron microscopic immunostaining for the prion protein (PrP) revealed a peculiar intraneuritic distribution in neocortical regions. Proteinase K resistant PrP (PrPres) was undetectable by Western blotting in frontal cortex from the three cases with frozen tissue, even after enrichment for PrPres by centrifugation or by phosphotungstic acid precipitation. Conformation-dependent immunoassay analysis using a range of PK digestion conditions (and no PK digestion) produced only very limited evidence of meaningful D-N (denatured/native) values, indicative of the presence of disease-associated PrP (PrPSc) in these cases, when the results were compared with appropriate negative control groups.

CONCLUSIONS: Our observation expands the spectrum of conditions associated with rapidly progressive dementia and may have implications for the understanding of the pathogenesis of prion diseases.

Original languageEnglish
Pages (from-to)72
Number of pages1
JournalActa neuropathologica communications
Volume1
Issue number1
DOIs
Publication statusPublished - 2013

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Endopeptidase K
Prion Diseases
Dementia
Digestion
Thalamic Diseases
Phosphotungstic Acid
Frontal Lobe
Centrifugation
Immunoassay
Western Blotting
Observation
Electrons
Light
Control Groups
Prion Proteins

ASJC Scopus subject areas

  • Medicine(all)

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Rapidly progressive dementia with thalamic degeneration and peculiar cortical prion protein immunoreactivity, but absence of proteinase K resistant PrP : a new disease entity? / Kovacs, Gabor G.; Peden, Alexander; Weis, Serge; Höftberger, Romana; Berghoff, Anna S.; Yull, Helen; Ströbel, Thomas; Koppi, Stefan; Katzenschlager, Regina; Langenscheidt, Dieter; Assar, Hamid; Zaruba, Elisabeth; Gröner, Albrecht; Voigtländer, Till; Puska, Gina; Hametner, Eva; Grams, Astrid; Muigg, Armin; Knoflach, Michael; László, L.; Ironside, James W.; Head, Mark W.; Budka, Herbert.

In: Acta neuropathologica communications, Vol. 1, No. 1, 2013, p. 72.

Research output: Contribution to journalArticle

Kovacs, GG, Peden, A, Weis, S, Höftberger, R, Berghoff, AS, Yull, H, Ströbel, T, Koppi, S, Katzenschlager, R, Langenscheidt, D, Assar, H, Zaruba, E, Gröner, A, Voigtländer, T, Puska, G, Hametner, E, Grams, A, Muigg, A, Knoflach, M, László, L, Ironside, JW, Head, MW & Budka, H 2013, 'Rapidly progressive dementia with thalamic degeneration and peculiar cortical prion protein immunoreactivity, but absence of proteinase K resistant PrP: a new disease entity?', Acta neuropathologica communications, vol. 1, no. 1, pp. 72. https://doi.org/10.1186/2051-5960-1-72
Kovacs, Gabor G. ; Peden, Alexander ; Weis, Serge ; Höftberger, Romana ; Berghoff, Anna S. ; Yull, Helen ; Ströbel, Thomas ; Koppi, Stefan ; Katzenschlager, Regina ; Langenscheidt, Dieter ; Assar, Hamid ; Zaruba, Elisabeth ; Gröner, Albrecht ; Voigtländer, Till ; Puska, Gina ; Hametner, Eva ; Grams, Astrid ; Muigg, Armin ; Knoflach, Michael ; László, L. ; Ironside, James W. ; Head, Mark W. ; Budka, Herbert. / Rapidly progressive dementia with thalamic degeneration and peculiar cortical prion protein immunoreactivity, but absence of proteinase K resistant PrP : a new disease entity?. In: Acta neuropathologica communications. 2013 ; Vol. 1, No. 1. pp. 72.
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T2 - a new disease entity?

AU - Kovacs, Gabor G.

AU - Peden, Alexander

AU - Weis, Serge

AU - Höftberger, Romana

AU - Berghoff, Anna S.

AU - Yull, Helen

AU - Ströbel, Thomas

AU - Koppi, Stefan

AU - Katzenschlager, Regina

AU - Langenscheidt, Dieter

AU - Assar, Hamid

AU - Zaruba, Elisabeth

AU - Gröner, Albrecht

AU - Voigtländer, Till

AU - Puska, Gina

AU - Hametner, Eva

AU - Grams, Astrid

AU - Muigg, Armin

AU - Knoflach, Michael

AU - László, L.

AU - Ironside, James W.

AU - Head, Mark W.

AU - Budka, Herbert

PY - 2013

Y1 - 2013

N2 - BACKGROUND: Human prion diseases are a group of rare fatal neurodegenerative conditions with well-developed clinical and neuropathological diagnostic criteria. Recent observations have expanded the spectrum of prion diseases beyond the classically recognized forms.RESULTS: In the present study we report six patients with a novel, apparently sporadic disease characterised by thalamic degeneration and rapidly progressive dementia (duration of illness 2-12 months; age at death: 55-81 years). Light and electron microscopic immunostaining for the prion protein (PrP) revealed a peculiar intraneuritic distribution in neocortical regions. Proteinase K resistant PrP (PrPres) was undetectable by Western blotting in frontal cortex from the three cases with frozen tissue, even after enrichment for PrPres by centrifugation or by phosphotungstic acid precipitation. Conformation-dependent immunoassay analysis using a range of PK digestion conditions (and no PK digestion) produced only very limited evidence of meaningful D-N (denatured/native) values, indicative of the presence of disease-associated PrP (PrPSc) in these cases, when the results were compared with appropriate negative control groups.CONCLUSIONS: Our observation expands the spectrum of conditions associated with rapidly progressive dementia and may have implications for the understanding of the pathogenesis of prion diseases.

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