Biomarkers and diagnostic guidelines for sporadic Creutzfeldt-Jakob disease

Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal and potentially transmissible neurodegenerative disease caused by misfolded prion proteins (PrP(Sc)). To date, effective therapeutics are not available and accurate diagnosis can be challenging. Clinical diagnostic criteria employ a combination of characteristic neuropsychiatric symptoms, cerebrospinal fluid (CSF) proteins 14–3-3, MRI, and EEG. Supportive biomarkers such as high CSF total Tau may aid the diagnostic process. Discordant results of studies however, have led to controversies about the clinical value of some 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 diagnosis of sCJD including RT-QuIC will 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 current investigation.