Advanced tests for early and accurate diagnosis of Creutzfeldt–Jakob disease
Key Points Early and accurate diagnosis of Creutzfeldt–Jakob disease (CJD) is essential to avoid iatrogenic transmission and to distinguish CJD from potentially treatable dementias Diagnosis of CJD in living patients is challenging, mainly because the disease phenotypes are highly heterogeneous, and...
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| Published in: | Nature reviews. Neurology Vol. 12; no. 6; pp. 325 - 333 |
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| Main Authors: | , , , |
| Format: | Journal Article |
| Language: | English |
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01.06.2016
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| ISSN: | 1759-4758, 1759-4766 |
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| Abstract | Key Points
Early and accurate diagnosis of Creutzfeldt–Jakob disease (CJD) is essential to avoid iatrogenic transmission and to distinguish CJD from potentially treatable dementias
Diagnosis of CJD in living patients is challenging, mainly because the disease phenotypes are highly heterogeneous, and detection of the misfolded protein in the brain tissue is often not feasible
Supportive investigations such as EEG, MRI and cerebrospinal fluid biomarkers have a relatively low diagnostic sensitivity and specificity in CJD
Diagnosis of CJD has been markedly improved by novel ultrasensitive seeding assays, such as real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA), which are based on amplified prion detection
RT-QuIC is specific and highly sensitive for sporadic CJD, whereas PMCA is extremely sensitive for detecting variant CJD prions in biological fluids and in extraneural or lymphatic tissues
In the future, novel assays analogous to RT-QuIC or PMCA might provide a protein-seeding-based diagnosis in other neurodegenerative diseases in which prion-like neurodegenerative processes are implicated
Diagnosis of Creutzfeldt–Jakob disease (CJD) in living patients is challenging, but distinguishing this untreatable disease from treatable rapidly progressive dementias is essential, and will also help prevent iatrogenic transmission of CJD. In this Review, Zanusso
et al
. discuss novel techniques, such as ultrasensitive protein seeding assays and nasal brushings, that can aid antemortem diagnosis of CJD.
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. |
|---|---|
| AbstractList | 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.sup.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.sup.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.sup.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. Key Points Early and accurate diagnosis of Creutzfeldt–Jakob disease (CJD) is essential to avoid iatrogenic transmission and to distinguish CJD from potentially treatable dementias Diagnosis of CJD in living patients is challenging, mainly because the disease phenotypes are highly heterogeneous, and detection of the misfolded protein in the brain tissue is often not feasible Supportive investigations such as EEG, MRI and cerebrospinal fluid biomarkers have a relatively low diagnostic sensitivity and specificity in CJD Diagnosis of CJD has been markedly improved by novel ultrasensitive seeding assays, such as real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA), which are based on amplified prion detection RT-QuIC is specific and highly sensitive for sporadic CJD, whereas PMCA is extremely sensitive for detecting variant CJD prions in biological fluids and in extraneural or lymphatic tissues In the future, novel assays analogous to RT-QuIC or PMCA might provide a protein-seeding-based diagnosis in other neurodegenerative diseases in which prion-like neurodegenerative processes are implicated Diagnosis of Creutzfeldt–Jakob disease (CJD) in living patients is challenging, but distinguishing this untreatable disease from treatable rapidly progressive dementias is essential, and will also help prevent iatrogenic transmission of CJD. In this Review, Zanusso et al . discuss novel techniques, such as ultrasensitive protein seeding assays and nasal brushings, that can aid antemortem diagnosis of CJD. 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. 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. |
| Audience | Academic |
| Author | Monaco, Salvatore Pocchiari, Maurizio Zanusso, Gianluigi Caughey, Byron |
| Author_xml | – sequence: 1 givenname: Gianluigi surname: Zanusso fullname: Zanusso, Gianluigi email: gianluigi.zanusso@univr.it organization: Department of Neurosciences, Biomedicine and Movement Sciences, Policlinico G.B. Rossi, University of Verona – sequence: 2 givenname: Salvatore surname: Monaco fullname: Monaco, Salvatore organization: Department of Neurosciences, Biomedicine and Movement Sciences, Policlinico G.B. Rossi, University of Verona – sequence: 3 givenname: Maurizio surname: Pocchiari fullname: Pocchiari, Maurizio organization: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità – sequence: 4 givenname: Byron surname: Caughey fullname: Caughey, Byron organization: Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27174240$$D View this record in MEDLINE/PubMed |
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Early and accurate diagnosis of Creutzfeldt–Jakob disease (CJD) is essential to avoid iatrogenic transmission and to distinguish CJD from... Early and accurate diagnosis of Creutzfeldt-Jakob disease (CJD) is a necessary to distinguish this untreatable disease from treatable rapidly progressive... |
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| Title | Advanced tests for early and accurate diagnosis of Creutzfeldt–Jakob disease |
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