A prognostic model for overall survival in sporadic Creutzfeldt‐Jakob disease

Llorens, Franc; Rübsamen, Nicole; Hermann, Péter; Schmitz, Matthias; Villar‐Piqué, Anna; Goebel, Stefan; Karch, André; Zerr, Inga

doi:10.1002/alz.12133

Cited by 28 publications

(33 citation statements)

References 30 publications

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“…66 CSF t-Tau has also become a candidate as predictor of survival time. 67 The p-Tau/t-Tau (or t-Tau/p-Tau) ratio is a very important alternative biomarker for sCJD. 66 It showed a very high diagnostic accuracy in the differentiation of sCJD from other neurological diseases (OND, AUC: 0•98), AD (AUC 0•99), 68 and rapidly progressive AD (AUC 0•99).…”

Section: Tau Proteinmentioning

confidence: 99%

“…• high sensitivity 37,51,52,60 • high specificity versus most neurodegenerative dementias 37,53,54 • moderate specificity versus acute events and encephalitis 63 • low specificity versus atypical AD [54][55][56] • moderate sensitivity for certain sCJD types 51,61 • different cut-offs in the literature 36,[64][65][66] • improved accuracy (p-Tau/t-Tau ratio) 65,67 • prognostic marker 66 • peripheral marker (blood-based) 18,19…”

Section: Taumentioning

confidence: 99%

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Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease

Hermann

Appleby

Brandel

et al. 2021

The Lancet Neurology

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Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal and potentially transmissible neurodegenerative disease caused by misfolded prion proteins. To date, effective therapeutics are not available and accurate diagnosis can be challenging. Clinical diagnostic criteria employ a combination of characteristic cerebrospinal fluid (CSF) 14-3-3 proteins, MRI findings, EEG changes, and neuropsychiatric symptoms. Supportive biomarkers such as high CSF total Tau may aid the diagnostic process. However, discordant results of studies have led to controversies about the clinical value of established surrogate biomarkers. The recent development and clinical application of disease-specific protein aggregation and amplification assays such as Real-time Quaking Induced Conversion (RT-QuIC) have constituted major breakthroughs for the confident pre-mortem diagnosis of sCJD. Updated criteria for the biomarker-based diagnosis of sCJD including RT-QuIC will improve early clinical confirmation, disease surveillance, assessment of potential tissue infectivity, and trial monitoring. Further, potential pre-symptomatic, prognostic, and blood-based biomarker candidates have been identified in recent years.

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Section: Tau Proteinmentioning

confidence: 99%

Section: Taumentioning

confidence: 99%

Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease

Hermann

Appleby

Brandel

et al. 2021

The Lancet Neurology

Self Cite

196

222

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show abstract

“…Although a test for in vivo PrP Sc typing is currently unavailable, codon 129 genotyping allows partial patient stratification since early disease onset. In this regard, multivariate analyses adjusted for age and codon 129 genotype showed that CSF and blood NfL, CSF tau, and CSF 14-3-3 were still predictive of survival (Staffaroni et al, 2019;Abu-Rumeileh et al, 2020a;Llorens et al, 2020a). Therefore, current evidence strongly recommends a stratification according to disease subtype or at least codon 129 genotype (in the clinical setting) to select outcomes and endpoints in future clinical trials (Abu-Rumeileh et al, 2020a).…”

Section: Prognostic Valuementioning

confidence: 99%

Cerebrospinal Fluid and Blood Neurofilament Light Chain Protein in Prion Disease and Other Rapidly Progressive Dementias: Current State of the Art

Abu‐Rumeileh

Parchi

2021

Front. Neurosci.

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Rapidly progressive dementia (RPD) is an umbrella term referring to several conditions causing a rapid neurological deterioration associated with cognitive decline and short disease duration. They comprise Creutzfeldt–Jakob disease (CJD), the archetypal RPD, rapidly progressive variants of the most common neurodegenerative dementias (NDs), and potentially treatable conditions such as infectious or autoimmune encephalitis and cerebrovascular disease. Given the significant clinical and, sometimes, neuroradiological overlap between these different disorders, biofluid markers also contribute significantly to the differential diagnosis. Among them, the neurofilament light chain protein (NfL) has attracted growing attention in recent years as a biofluid marker of neurodegeneration due to its sensitivity to axonal damage and the reliability of its measurement in both cerebrospinal fluid (CSF) and blood. Here, we summarize current knowledge regarding biological and clinical implications of NfL evaluation in biofluids across RPDs, emphasizing CJD, and other prion diseases. In the latter, NfL demonstrated a good diagnostic and prognostic accuracy and a potential value as a marker of proximity to clinical onset in pre-symptomatic PRNP mutation carriers. Similarly, in Alzheimer’s disease and other NDs, higher NfL concentrations seem to predict a faster disease progression. While increasing evidence indicates a potential clinical value of NfL in monitoring cerebrovascular disease, the association between NfL and prediction of outcome and/or disease activity in autoimmune encephalitis and infectious diseases has only been investigated in few cohorts and deserves confirmatory studies. In the era of precision medicine and evolving therapeutic options, CSF and blood NfL might aid the diagnostic and prognostic assessment of RPDs and the stratification and management of patients according to disease progression in clinical trials.

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“…Therefore, they are not yet included in clinical practice. Importantly, the use of surrogate CSF biomarkers is not limited to diagnostic purposes; rather, a potential use as prognostic, predictive, monitoring, and response biomarkers has been proposed [ 35 , 46 , 65 , 71 ]. Therefore, the characterization of the best putative application for each biomarker as well as the identification of biomarkers targeting the complete pathological signatures of prion disease will greatly enhance the rational development and interpretation of future therapeutic interventions.…”

Section: Introductionmentioning

confidence: 99%

TREM2 expression in the brain and biological fluids in prion diseases

et al. 2021

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Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune cell surface receptor that regulates microglial function and is involved in the pathophysiology of several neurodegenerative diseases. Its soluble form (sTREM2) results from shedding of the TREM2 ectodomain. The role of TREM2 in prion diseases, a group of rapidly progressive dementias remains to be elucidated. In the present study, we analysed the expression of TREM2 and its main sheddase ADAM10 in the brain of sporadic Creutzfeldt-Jakob disease (sCJD) patients and evaluated the role of CSF and plasma sTREM2 as a potential diagnostic marker of prion disease. Our data indicate that, compared to controls, TREM2 is increased in sCJD patient brains at the mRNA and protein levels in a regional and subtype dependent fashion, and expressed in a subpopulation of microglia. In contrast, ADAM10 is increased at the protein, but not the mRNA level, with a restricted neuronal expression. Elevated CSF sTREM2 is found in sCJD, genetic CJD with mutations E200K and V210I in the prion protein gene (PRNP), and iatrogenic CJD, as compared to healthy controls (HC) (AUC = 0.78–0.90) and neurological controls (AUC = 0.73–0.85), while CSF sTREM2 is unchanged in fatal familial insomnia. sTREM2 in the CSF of cases with Alzheimer’s disease, and multiple sclerosis was not significantly altered in our series. CSF sTREM2 concentrations in sCJD are PRNP codon 129 and subtype-related, correlate with CSF 14-3-3 positivity, total-tau and YKL-40, and increase with disease progression. In plasma, sTREM2 is increased in sCJD compared with HC (AUC = 0.80), displaying positive correlations with plasma total-tau, neurofilament light, and YKL-40. We conclude that comparative study of TREM2 in brain and biological fluids of prion diseases reveals TREM2 to be altered in human prion diseases with a potential value in target engagement, patient stratification, and disease monitoring.

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A prognostic model for overall survival in sporadic Creutzfeldt‐Jakob disease

Cited by 28 publications

References 30 publications

Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease

Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease

Cerebrospinal Fluid and Blood Neurofilament Light Chain Protein in Prion Disease and Other Rapidly Progressive Dementias: Current State of the Art

TREM2 expression in the brain and biological fluids in prion diseases

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