title: Transmission characteristics of variably protease-sensitive prionopathy.
abstract: Variably protease-sensitive prionopathy (VPSPr), a recently identified and seemingly sporadic human prion disease, is distinct from Creutzfeldt-Jakob disease (CJD) but shares features of Gerstmann-Sträussler-Scheinker disease (GSS). However, contrary to exclusively inherited GSS, no prion protein (PrP) gene variations have been detected in VPSPr, suggesting that VPSPr might be the long-sought sporadic form of GSS. The VPSPr atypical features raised the issue of transmissibility, a prototypical property of prion diseases. We inoculated VPSPr brain homogenate into transgenic mice expressing various levels of human PrP (PrPC). On first passage, 54% of challenged mice showed histopathologic lesions, and 34% harbored abnormal PrP similar to that of VPSPr. Surprisingly, no prion disease was detected on second passage. We concluded that VPSPr is transmissible; thus, it is an authentic prion disease. However, we speculate that normal human PrPC is not an efficient conversion substrate (or mouse brain not a favorable environment) and therefore cannot sustain replication beyond the first passage.
authors.forename: Silvio
authors.initials: S
authors.lastname: Notari
authors.forename: Xiangzhu
authors.initials: X
authors.lastname: Xiao
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Espinosa
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Cohen
authors.forename: Liuting
authors.initials: L
authors.lastname: Qing
authors.forename: Patricia
authors.initials: P
authors.lastname: Aguilar-Calvo
authors.forename: Diane
authors.initials: D
authors.lastname: Kofskey
authors.forename: Ignazio
authors.initials: I
authors.lastname: Cali
authors.forename: Laura
authors.initials: L
authors.lastname: Cracco
authors.forename: Qingzhong
authors.initials: Q
authors.lastname: Kong
authors.forename: Juan Maria
authors.initials: JM
authors.lastname: Torres
authors.forename: Wenquan
authors.initials: W
authors.lastname: Zou
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Gambetti
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000473:pathology; D017096:Prion Diseases / Q000235:genetics / Q000473:pathology / Q000635:transmission*; D011328:Prions / Q000235:genetics / Q000378:metabolism
chemical_list: D011328:Prions