title: Advanced tests for early and accurate diagnosis of Creutzfeldt-Jakob disease.
abstract: Early and accurate diagnosis of Creutzfeldt-Jakob disease (CJD) is a necessary to distinguish this untreatable disease from treatable rapidly progressive dementias, and to prevent iatrogenic transmission. Currently, definitive diagnosis of CJD requires detection of the abnormally folded, CJD-specific form of protease-resistant prion protein (PrP(CJD)) in brain tissue obtained postmortem or via biopsy; therefore, diagnosis of sporadic CJD in clinical practice is often challenging. Supporting investigations, including MRI, EEG and conventional analyses of cerebrospinal fluid (CSF) biomarkers, are helpful in the diagnostic work-up, but do not allow definitive diagnosis. Recently, novel ultrasensitive seeding assays, based on the amplified detection of PrP(CJD), have improved the diagnostic process; for example, real-time quaking-induced conversion (RT-QuIC) is a sensitive method to detect prion-seeding activity in brain homogenate from humans with any subtype of sporadic CJD. RT-QuIC can also be used for in vivo diagnosis of CJD: its diagnostic sensitivity in detecting PrP(CJD) in CSF samples is 96%, and its specificity is 100%. Recently, we provided evidence that RT-QuIC of olfactory mucosa brushings is a 97% sensitive and 100% specific for sporadic CJD. These assays provide a basis for definitive antemortem diagnosis of prion diseases and, in doing so, improve prospects for reducing the risk of prion transmission. Moreover, they can be used to evaluate outcome measures in therapeutic trials for these as yet untreatable infections.
authors.affiliation: Department of Neurosciences, Biomedicine and Movement Sciences, Policlinico G.B. Rossi, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Zanusso
authors.affiliation: Department of Neurosciences, Biomedicine and Movement Sciences, Policlinico G.B. Rossi, University of Verona, Piazzale L.A. Scuro 10, 37134 Verona, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Monaco
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pocchiari
authors.affiliation: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, 903 4th Street, Hamilton, 59840 Montana, USA.
authors.forename: Byron
authors.initials: B
authors.lastname: Caughey
mesh_terms: D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis*; D042241:Early Diagnosis; D006801:Humans; D025202:Molecular Diagnostic Techniques