title: Atypical prion protein conformation in familial prion disease with PRNP P105T mutation.
abstract: Protease-resistant prion protein (PrP(Sc) ) is diagnostic of prion disease, yet its detection is frequently difficult. Here, we describe a patient with a PRNP P105T mutation and typical familial prion disease. Brain PrP(Sc) was undetectable by conventional Western blotting and barely detectable after phosphotungstate precipitation, where it displayed an atypical pattern suggestive of noncanonical conformation. Therefore, we used a novel misfolded protein assay (MPA) that detects PrP aggregates independently of their protease resistance. The MPA revealed the presence of aggregated PrP in similar amounts as in typical sporadic Creutzfeldt-Jakob disease. These findings suggest that measurements of PrP aggregation with the MPA may be potentially more sensitive than protease-based methodologies.
authors.affiliation: Department of Neurology, Institute of Neuropathology, University Hospital Zurich and Basel, Switzerland.
authors.forename: Magdalini
authors.initials: M
authors.lastname: Polymenidou
authors.forename: Stefan
authors.initials: S
authors.lastname: Prokop
authors.forename: Hans H
authors.initials: HH
authors.lastname: Jung
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Hewer
authors.forename: David
authors.initials: D
authors.lastname: Peretz
authors.forename: Rita
authors.initials: R
authors.lastname: Moos
authors.forename: Markus
authors.initials: M
authors.lastname: Tolnay
authors.forename: Adriano
authors.initials: A
authors.lastname: Aguzzi
mesh_terms: D000328:Adult; D001483:Base Sequence; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D017096:Prion Diseases / Q000175:diagnosis* / Q000235:genetics*; D000072002:Prion Proteins; D011328:Prions / Q000032:analysis* / Q000235:genetics*
chemical_list: C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions