Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease

Peter Hermann; Brian Appleby; Jean-Philippe Brandel; Byron Caughey; Steven Collins; Michael D Geschwind; Alison Green; Stephane Haïk; Gabor G Kovacs; Anna Ladogana; Franc Llorens; Simon Mead; Noriyuki Nishida; Suvankar Pal; Piero Parchi; Maurizio Pocchiari; Katsuya Satoh; Gianluigi Zanusso; Inga Zerr

doi:10.1016/S1474-4422(20)30477-4

Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease

Lancet Neurol. 2021 Mar;20(3):235-246. doi: 10.1016/S1474-4422(20)30477-4.

Authors

Peter Hermann¹, Brian Appleby², Jean-Philippe Brandel³, Byron Caughey⁴, Steven Collins⁵, Michael D Geschwind⁶, Alison Green⁷, Stephane Haïk³, Gabor G Kovacs⁸, Anna Ladogana⁹, Franc Llorens¹⁰, Simon Mead¹¹, Noriyuki Nishida¹², Suvankar Pal⁷, Piero Parchi¹³, Maurizio Pocchiari⁹, Katsuya Satoh¹⁴, Gianluigi Zanusso¹⁵, Inga Zerr¹⁶

Affiliations

¹ National Reference Center for Transmissible Spongiform Encephalopathies, Department of Neurology, University Medical Center Göttingen, Göttingen, Germany. Electronic address: peter.hermann@med.uni-goettingen.de.
² National Prion Disease Pathology Surveillance Center, Case Western Reserve University, Cleveland, OH, USA; Departments of Neurology, Psychiatry, and Pathology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA.
³ Cellule Nationale de Référence des Maladies de Creutzfeldt-Jakob, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; Institut du Cerveau et de la Moelle épinière, Sorbonne Université, Paris, France.
⁴ Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute for Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
⁵ Australian National Creutzfeldt-Jakob disease Registry, Florey Institute of Neuroscience and Mental Health and Department of Medicine, University of Melbourne, Parkville, VIC, Australia.
⁶ Department of Neurology, University of California, San Francisco, CA, USA.
⁷ National CJD Research & Surveillance Unit, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
⁸ Tanz Centre for Research in Neurodegenerative Disease and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; Laboratory Medicine Program, University Health Network, Toronto, ON, Canada.
⁹ Department of Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
¹⁰ National Reference Center for Transmissible Spongiform Encephalopathies, Department of Neurology, University Medical Center Göttingen, Göttingen, Germany; Network Center For Biomedical Research Of Neurodegenerative Diseases, Institute Carlos III, L'Hospitalet de Llobregat, Barcelona, Spain; Bellvitge Biomedical Research Institute, Hospitalet de Llobregat, Barcelona, Spain.
¹¹ National Prion Clinic, University College London Hospitals NHS Foundation Trust, London, UK; Medical Research Council Prion Unit at University College London, Institute of Prion Diseases, London, UK.
¹² Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
¹³ Istituto di Ricovero e Cura e Carattere Scientifico, Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy; Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy.
¹⁴ Department of Locomotive Rehabilitation Science, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
¹⁵ Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
¹⁶ National Reference Center for Transmissible Spongiform Encephalopathies, Department of Neurology, University Medical Center Göttingen, Göttingen, Germany; German Center for Neurodegenerative Diseases, Göttingen, Germany.

Abstract

Sporadic Creutzfeldt-Jakob disease is a fatal neurodegenerative disease caused by misfolded prion proteins (PrP^Sc). Effective therapeutics are currently not available and accurate diagnosis can be challenging. Clinical diagnostic criteria use a combination of characteristic neuropsychiatric symptoms, CSF proteins 14-3-3, MRI, and EEG. Supportive biomarkers, such as high CSF total tau, could aid the diagnostic process. However, discordant studies have led to controversies about the clinical value of some established surrogate biomarkers. 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 sporadic Creutzfeldt-Jakob disease. Updated criteria for the diagnosis of sporadic Creutzfeldt-Jakob disease, including application of RT-QuIC, should improve early clinical confirmation, surveillance, assessment of PrP^Sc seeding activity in different tissues, and trial monitoring. Moreover, emerging blood-based, prognostic, and potentially pre-symptomatic biomarker candidates are under investigation.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Biomarkers / analysis*
Creutzfeldt-Jakob Syndrome / diagnosis*
Creutzfeldt-Jakob Syndrome / diagnostic imaging
Creutzfeldt-Jakob Syndrome / genetics
Genetic Markers
Guidelines as Topic
Humans
Neuroimaging
Sensitivity and Specificity

Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease

Authors

Affiliations

Abstract

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MeSH terms

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Supplementary concepts

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