Diagnostic value of surrogate CSF biomarkers for Creutzfeldt–Jakob disease in the era of RT-QuIC

Abu‐Rumeileh, Samir; Baiardi, Simone; Polischi, Barbara; Mammana, Angela; Franceschini, Alessia; Green, Alison; Capellari, Sabina; Parchi, Piero

doi:10.1007/s00415-019-09537-0

Cited by 50 publications

(110 citation statements)

References 29 publications

Supporting

Mentioning

102

Contrasting

Order By: Relevance

“…Importantly, 14-3-3 quantification with ELISA (sensitivity 95.2%) out-performed WB, displaying the highest sensitivity among the biomarkers herein tested. Since the development of the 14-3-3 ELISA, several studies in large cohorts of sCJD cases have demonstrated superior sensitivity compared to the WB method [24,[40][41][42], but this is the first study to validate this observation in iCJD.…”

Section: Discussionmentioning

confidence: 80%

Diagnostic Accuracy of Prion Disease Biomarkers in Iatrogenic Creutzfeldt-Jakob Disease

Llorens

Villar‐Piqué

Hermann³

et al. 2020

Biomolecules

View full text Add to dashboard Cite

Human prion diseases are classified into sporadic, genetic, and acquired forms. Within this last group, iatrogenic Creutzfeldt–Jakob disease (iCJD) is caused by human-to-human transmission through surgical and medical procedures. After reaching an incidence peak in the 1990s, it is believed that the iCJD historical period is probably coming to an end, thanks to lessons learnt from past infection sources that promoted new prion prevention and decontamination protocols. At this point, we sought to characterise the biomarker profile of iCJD and compare it to that of sporadic CJD (sCJD) for determining the value of available diagnostic tools in promptly recognising iCJD cases. To that end, we collected 23 iCJD samples from seven national CJD surveillance centres and analysed the electroencephalogram and neuroimaging data together with a panel of seven CSF biomarkers: 14-3-3, total tau, phosphorylated/total tau ratio, alpha-synuclein, neurofilament light, YKL-40, and real-time quaking induced conversion of prion protein. Using the cut-off values established for sCJD, we found the sensitivities of these biomarkers for iCJD to be similar to those described for sCJD. Given the limited relevant information on this issue to date, the present study validates the use of current sCJD biomarkers for the diagnosis of future iCJD cases.

show abstract

Section: Discussionmentioning

confidence: 80%

Diagnostic Accuracy of Prion Disease Biomarkers in Iatrogenic Creutzfeldt-Jakob Disease

Llorens

Villar‐Piqué

Hermann³

et al. 2020

Biomolecules

View full text Add to dashboard Cite

show abstract

“…Total tau has been found to have 91% sensitivity and 79% specificity in the diagnosis of CJD which is better than CSF 14-3-3 test. 17 Similarly, high CSF NfL level has been found in CJD in comparison to other neurodegenerative dementias. 18 Although NfL is the most sensitive (>95%) biomarker for CJD, its specificity is only about 43%.…”

Section: F I G U R E 3 Mri With T2 Flair Image Shows Bilateral Symmetmentioning

confidence: 93%

“…18 Although NfL is the most sensitive (>95%) biomarker for CJD, its specificity is only about 43%. 17 Thus, CSF total tau is the recommended CSF biomarkers alternative to RT-QuIC assay for the diagnosis of CJD.…”

Section: F I G U R E 3 Mri With T2 Flair Image Shows Bilateral Symmetmentioning

confidence: 99%

Sporadic Creutzfeldt‐Jakob disease: A case report and review of literature

Ojha

Nepal

Jamarkattel

et al. 2020

Clinical Case Reports

View full text Add to dashboard Cite

Creutzfeldt-Jakob disease (CJD) is a rare and fatal human neurodegenerative disorder characterized by a rapidly progressive dementia, myoclonus, cerebellar, pyramidal, extrapyramidal, visual symptoms, and psychiatric manifestations. CJD occur sporadically in about 85% of cases, 10%-15% are inherited, <1% are iatrogenic, and <1% are variant. 1,2 Normal cellular prion protein (PrPC) is found on cell membranes throughout the mammalian body. Disease-causing form of prion (PrPSc) multiplies by binding to the normal cellular isoform PrP and converts it into an abnormal, structurally altered disease-causing PrPSc, which then spreads and accumulates throughout the brain leading to spongiform neurodegeneration. 1 CJD occurs worldwide, but as systematic surveillance has only been undertaken in a minority of countries, the incidence in much of the world is currently unknown. 3,4 Usually, initial diagnosis of CJD may be obscured by its variable presentation. We herein present a case of a 66-year-old female who was admitted to our university hospital for a rapidly progressive cognitive decline followed by ataxia and myoclonus. She was diagnosed with sporadic CJD, based on her clinical features, cerebrospinal fluid (CSF) studies, electroencephalogram (EEG), and brain magnetic resonance imaging (MRI) imaging sequences. 2 | CASE DESCRIPTION A 66-year-old female was referred to our hospital with 4-month history of progressive cognitive decline, behavioral, and personality changes. She was in her usual state of health until four months ago when she was noted by her family members to have easy forgetfulness and worsening functional impairment. She was initially noted to be aggressive and stopped taking care of herself. As per the husband, she would have sudden outbursts of agitation and delusional behavior followed by paranoid behavior. She initially presented

show abstract

“…Being in direct contact with the CNS and easily accessible via lumbar puncture, the cerebrospinal fluid has become the preferred site for early detection of PrP Sc , which has led to the adaptation of in vitro prion propagation techniques to this body fluid. As mentioned above, the CSF is being used extensively in TSE diagnostic for the detection of surrogate biomarkers of neuronal damage that includes an increasing number of proteins, the levels of which are altered in prion disorders, and that have been extensively reviewed elsewhere [9,[69][70][71][72]. However, the change in the levels of many of such surrogate markers are also detected in other neurodegenerative diseases, which complicates the differential diagnosis and requires a protein profiling and checking a panel of the relative levels of multiple biomarkers [71].…”

Section: Detection Of Prp Sc In Cerebrospinal Fluidmentioning

confidence: 99%

“…The increasing but still small number of laboratories using this method at present for diagnosis, in many cases depend on external supply of recombinant protein to be used as substrate, that among other technical variations may cause low reproducibility between different labs. The inter-laboratory reproducibility using different protein suppliers and distinct batches has been recently addressed showing good results in a small cohort of CSF samples analyzed by 11 different laboratories worldwide [109], but needs to be further assessed [9]. Finally, another problem that affects not only RT-QuIC, but also any other method for prion detection in CSF, is the ignorance of how long, prior to the onset of clinical signs, is PrP Sc detectable in this body fluid, which will be of utmost importance for the pre-clinical detection of the disease in genetic cases when a therapy is finally available.…”

Section: Prp Sc In Csf In Human Prion Diseasesmentioning

confidence: 99%

Detection of Pathognomonic Biomarker PrPSc and the Contribution of Cell Free-Amplification Techniques to the Diagnosis of Prion Diseases

et al. 2020

View full text Add to dashboard Cite

Transmissible spongiform encephalopathies or prion diseases are rapidly progressive neurodegenerative diseases, the clinical manifestation of which can resemble other promptly evolving neurological maladies. Therefore, the unequivocal ante-mortem diagnosis is highly challenging and was only possible by histopathological and immunohistochemical analysis of the brain at necropsy. Although surrogate biomarkers of neurological damage have become invaluable to complement clinical data and provide more accurate diagnostics at early stages, other neurodegenerative diseases show similar alterations hindering the differential diagnosis. To solve that, the detection of the pathognomonic biomarker of disease, PrP Sc , the aberrantly folded isoform of the prion protein, could be used. However, the amounts in easily accessible tissues or body fluids at pre-clinical or early clinical stages are extremely low for the standard detection methods. The solution comes from the recent development of in vitro prion propagation techniques, such as Protein Misfolding Cyclic Amplification (PMCA) and Real Time-Quaking Induced Conversion (RT-QuIC), which have been already applied to detect minute amounts of PrP Sc in different matrixes and make early diagnosis of prion diseases feasible in a near future. Herein, the most relevant tissues and body fluids in which PrP Sc has been detected in animals and humans are being reviewed, especially those in which cell-free prion propagation systems have been used with diagnostic purposes.

show abstract

Diagnostic value of surrogate CSF biomarkers for Creutzfeldt–Jakob disease in the era of RT-QuIC

Cited by 50 publications

References 29 publications

Diagnostic Accuracy of Prion Disease Biomarkers in Iatrogenic Creutzfeldt-Jakob Disease

Diagnostic Accuracy of Prion Disease Biomarkers in Iatrogenic Creutzfeldt-Jakob Disease

Sporadic Creutzfeldt‐Jakob disease: A case report and review of literature

Detection of Pathognomonic Biomarker PrPSc and the Contribution of Cell Free-Amplification Techniques to the Diagnosis of Prion Diseases

Contact Info

Product

Resources

About