• Fabio Moda, Pierluigi Gambetti, Silvio Notari, Luis Concha-Marambio, Marcella Catania, Kyung-Won Park, Emanuela Maderna, Silvia Suardi, Stéphane Haïk, Jean-Philippe Brandel, James Ironside, Richard Knight, Fabrizio Tagliavini, and Claudio Soto.
• From the Mitchell Center for Research in Alzheimer's Disease and Related Brain Disorders, University of Texas Medical School at Houston, Houston (F.M., L.C.-M., K.-W.P., C.S.); Foundation Carlo Besta Neurologic Institute, Milan (F.M., M.C., E.M., S.S., F.T.); National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland (P.G., S.N.); Universidad de los Andes, Facultad de Medicina, Santiago, Chile (L.C.-M.); Assistance Publique-Hôpitaux de Paris, Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob, Groupe Hospitalier Pitié-Salpêtrière, INSERM Unité 1127, Université Pierre et Marie Curie-Paris 6, and Centre Nationale de la Recherche Scientifique, Unité Mixte de Recherche - all in Paris (S.H., J.-P.B.); and the National CJD Research and Surveillance Unit, Western General Hospital, University of Edinburgh, Edinburgh (J.I., R.K.).
• N. Engl. J. Med. 2014 Aug 7; 371 (6): 530-9.

BackgroundPrions, the infectious agents responsible for transmissible spongiform encephalopathies, consist mainly of the misfolded prion protein (PrP(Sc)). The unique mechanism of transmission and the appearance of a variant form of Creutzfeldt-Jakob disease, which has been linked to consumption of prion-contaminated cattle meat, have raised concerns about public health. Evidence suggests that variant Creutzfeldt-Jakob disease prions circulate in body fluids from people in whom the disease is silently incubating.MethodsTo investigate whether PrP(Sc) can be detected in the urine of patients with variant Creutzfeldt-Jakob disease, we used the protein misfolding cyclic amplification (PMCA) technique to amplify minute quantities of PrP(Sc), enabling highly sensitive detection of the protein. We analyzed urine samples from several patients with various transmissible spongiform encephalopathies (variant and sporadic Creutzfeldt-Jakob disease and genetic forms of prion disease), patients with other degenerative or nondegenerative neurologic disorders, and healthy persons.ResultsPrP(Sc) was detectable only in the urine of patients with variant Creutzfeldt-Jakob disease and had the typical electrophoretic profile associated with this disease. PrP(Sc) was detected in 13 of 14 urine samples obtained from patients with variant Creutzfeldt-Jakob disease and in none of the 224 urine samples obtained from patients with other neurologic diseases and from healthy controls, resulting in an estimated sensitivity of 92.9% (95% confidence interval [CI], 66.1 to 99.8) and a specificity of 100.0% (95% CI, 98.4 to 100.0). The PrP(Sc) concentration in urine calculated by means of quantitative PMCA was estimated at 1×10(-16) g per milliliter, or 3×10(-21) mol per milliliter, which extrapolates to approximately 40 to 100 oligomeric particles of PrP(Sc) per milliliter of urine.ConclusionsUrine samples obtained from patients with variant Creutzfeldt-Jakob disease contained minute quantities of PrP(Sc). (Funded by the National Institutes of Health and others.).

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