title: Rapidly progressive dementia with thalamic degeneration and peculiar cortical prion protein immunoreactivity, but absence of proteinase K resistant PrP: a new disease entity?
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.
authors.affiliation: Institute of Neurology, Medical University of Vienna and Austrian Reference Centre for Human Prion Diseases Vienna, Vienna, Austria. gabor.kovacs@meduniwien.ac.at.
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Kovacs
authors.forename: Alexander
authors.initials: A
authors.lastname: Peden
authors.forename: Serge
authors.initials: S
authors.lastname: Weis
authors.forename: Romana
authors.initials: R
authors.lastname: Höftberger
authors.forename: Anna S
authors.initials: AS
authors.lastname: Berghoff
authors.forename: Helen
authors.initials: H
authors.lastname: Yull
authors.forename: Thomas
authors.initials: T
authors.lastname: Ströbel
authors.forename: Stefan
authors.initials: S
authors.lastname: Koppi
authors.forename: Regina
authors.initials: R
authors.lastname: Katzenschlager
authors.forename: Dieter
authors.initials: D
authors.lastname: Langenscheidt
authors.forename: Hamid
authors.initials: H
authors.lastname: Assar
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Zaruba
authors.forename: Albrecht
authors.initials: A
authors.lastname: Gröner
authors.forename: Till
authors.initials: T
authors.lastname: Voigtländer
authors.forename: Gina
authors.initials: G
authors.lastname: Puska
authors.forename: Eva
authors.initials: E
authors.lastname: Hametner
authors.forename: Astrid
authors.initials: A
authors.lastname: Grams
authors.forename: Armin
authors.initials: A
authors.lastname: Muigg
authors.forename: Michael
authors.initials: M
authors.lastname: Knoflach
authors.forename: Lajos
authors.initials: L
authors.lastname: László
authors.forename: James W
authors.initials: JW
authors.lastname: Ironside
authors.forename: Mark W
authors.initials: MW
authors.lastname: Head
authors.forename: Herbert
authors.initials: H
authors.lastname: Budka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D003704:Dementia / Q000473:pathology / Q000503:physiopathology*; D018450:Disease Progression; D019286:Endopeptidase K / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000503:physiopathology*; D011328:Prions / Q000378:metabolism*; D013788:Thalamus / Q000473:pathology / Q000503:physiopathology*
chemical_list: D011328:Prions; D019286:Endopeptidase K