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, Lajos LászlóJames W Ironside, Mark W Head, Herbert Budka

Research output: Contribution to journalArticlepeer-review

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
JournalActa Neuropathologica Communications
Volume1
Issue number1
DOIs
Publication statusPublished - 11 Nov 2013

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