Journal of Molecular Neuroscience

, Volume 45, Issue 3, pp 422–424 | Cite as

Variably Protease-Sensitive Prionopathy: a Novel Disease of the Prion Protein

  • Pierluigi Gambetti
  • Gianfranco Puoti
  • Wen-Quan Zou


Variably protease-sensitive prionopathy (VPSPr) is a novel disease involving the prion protein (PrP) that has clinical similarities with non-Alzheimer’s dementias especially frontotemporal dementia, diffuse Lewis body disease, and normal pressure hydrocephalus. VPSPr can be distinguished from sporadic Creutzfeldt–Jakob disease (sCJD) especially for the characteristics of the abnormal PrP. Furthermore, although VPSPr like sCJD affects patients with the three PrP genotypes as determined by the common methionine/valine polymorphism, the allelic prevalence is very different in the two diseases. These findings suggest that VPSPr is basically different from classical prion diseases such as sCJD being perhaps more akin to other neurodegenerative dementias.


Variably protease-sensitive prionopathy Prions Prion protein Prion diseases Creutzfeldt–Jakob disease Alzheimer’s disease 



This study was supported by the grants (to P.G.) from the National Institutes of Health (NIH) AG14359 and AG08702, the Centers for Disease Control and Prevention (CCU 515004), and the Britton Fund, and by grants (to W.Q.Z.) from NIH R01NS062787, the CJD Foundation, Alliance BioSecure, and the University Center on Aging and Health with the support of the McGregor Foundation and the President’s Discretionary Fund (Case Western Reserve University).


  1. Clavaguera F, Bolmont T, Crowther RA et al (2009) Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol 11:909–913PubMedCrossRefGoogle Scholar
  2. Collinge J, Palmer MS, Dryden AJ (1991) Genetic predisposition to iatrogenic Creutzfeldt-Jakob disease. Lancet 337:1441–1442PubMedCrossRefGoogle Scholar
  3. Gambetti P, Dong Z, Yuan J et al (2008) A novel human disease with abnormal prion protein sensitive to protease. Ann Neurol 63(6):697–708PubMedCrossRefGoogle Scholar
  4. Goedert M, Clavaguera F, Tolnay M (2010) The propagation of prion-like protein inclusions in neurodegenerative diseases. Trends Neurosci 33(7):317–325PubMedCrossRefGoogle Scholar
  5. Head MW, Knight R, Zeidler M, Yull H, Barlow A, Ironside JW (2009) A case of protease sensitive prionopathy in a patient in the UK. Neuropathol Appl Neurobiol 35(6):628–632PubMedCrossRefGoogle Scholar
  6. Head MW, Lowrie S, Chohan G, Knight R, Scoones DJ, Ironside JW (2010) Variably protease-sensitive prionopathy in a PRNP codon 129 heterozygous UK patient with co-existing tau, α synuclein and Aβ pathology. Acta Neuropath 120(6):821–823PubMedCrossRefGoogle Scholar
  7. Jansen C, Head MW, van Gool WA, Baas F, Yull H, Ironside JW, Rozemuller AJ (2010) The first case of protease-sensitive prionopathy (PSPr) in the Netherlands: a patient with an unusual GSS-like clinical phenotype. J Neurol Neurosurg Psychiatry 81(9):1052–1055PubMedCrossRefGoogle Scholar
  8. Kong Q, Surewicz WK, Petersen RB et al (2004) Inherited prion diseases. In: Prusiner SB (ed) Prion biology and diseases. Cold Spring Harbor Laboratory Press, New York, pp 673–775Google Scholar
  9. Rodríguez-Martínez AB, Garrido JM, Zarranz JJ et al (2010) A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: case report. BMC Neurol 10:99PubMedCrossRefGoogle Scholar
  10. Selkoe DJ, Podlisny MB (2002) Deciphering the genetic basis of Alzheimer’s disease. Annu Rev Genomics Hum Genet 3:67–99PubMedCrossRefGoogle Scholar
  11. Windl O, Dempster M, Estibeiro JP, Lathe et al (1996) Genetic basis of Creutzfeldt-Jakob disease in the United Kingdom: a systematic analysis of predisposing mutations and allelic variation in the PRNP gene. Hum Genet 98(3):259–264PubMedCrossRefGoogle Scholar
  12. Yuan J, Dong Z, Guo JP et al (2008) Accessibility of a critical prion protein region involved in strain recognition and its implications for the early detection of prions. Cell Mol Life Sci 65:631–643PubMedCrossRefGoogle Scholar
  13. Zou WQ, Puoti G, Xiao X et al (2010a) Variably protease-sensitive prionopathy: a new sporadic disease of the prion protein. Ann Neurol 68:162–172PubMedCrossRefGoogle Scholar
  14. Zou WQ, Langeveld J, Xiao X et al (2010b) PrP conformational transitions alter species preference of a PrP-specific antibody. J Biol Chem 285:13874–13884PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Pierluigi Gambetti
    • 1
    • 2
  • Gianfranco Puoti
    • 1
  • Wen-Quan Zou
    • 1
  1. 1.Department of Pathology, National Prion Disease Pathology Surveillance Center, School of MedicineCase Western Reserve UniversityClevelandUSA
  2. 2.Institute of Pathology, School of MedicineCase Western Reserve UniversityClevelandUSA

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