Advances in biomarkers for diagnosis and prognosis of prion diseases

Seeded amplification assays have improved the accuracy of the diagnosis of prion diseases, and blood-based diagnostic biomarkers are now close to clinical application. Although clinical diagnosis can be accurate, research on biomarkers is still crucial for therapeutic development and studies are addressing their use at preclinical stages in mutation carriers, focusing on non-invasive sampling. Some biomarkers have been tested in blood, tear fluids, and urine and could become easily accessible testing platforms. Emerging biomarkers can predict the onset or reflect the clinical course of prion disease, and might become crucial for the evaluation of new therapeutics. Furthermore, detection of misfolded prion protein at preclinical stages in healthy mutation carriers warrants a comprehensive discussion of associations with other molecular signals that might be also detectable before disease onset. A new disease staging system based on biomarkers should be evaluated in future clinical studies.