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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Bibliographic Details
Published in:Nature reviews. Neurology Vol. 12; no. 6; pp. 325 - 333
Main Authors: Zanusso, Gianluigi, Monaco, Salvatore, Pocchiari, Maurizio, Caughey, Byron
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01.06.2016
Nature Publishing Group
Subjects:
692/308/53/2421
692/699/375/365/1937
Analysis
Biomarkers
Care and treatment
Cerebrospinal fluid
Complications and side effects
Creutzfeldt-Jakob disease
Creutzfeldt-Jakob Syndrome - diagnosis
Dementia
Diagnosis
Diagnostic imaging
Early Diagnosis
Humans
Iatrogenesis
Laboratories
Medical prognosis
Medicine & Public Health
Molecular Diagnostic Techniques
Neurology
Neurosciences
Physiology, Pathological
Proteins
review-article
ISSN:1759-4758, 1759-4766
Online Access:Get full text
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Summary: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.
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ISSN:1759-4758
1759-4766
DOI:10.1038/nrneurol.2016.65