Introduction: Human prion diseases (PrDs) are transmissible fatal nervous system disorders with public health implications. They are characterized by the presence of a disease-associated form of the physiological cellular prion protein. Development of diagnostic procedures is important to avoid transmission, including through blood products. Methods used for the detection of disease-associated PrP have implications for other neurodegenerative diseases.
Areas covered: In this review, the authors discuss recent progress in the understanding of the molecular background of phenotypic variability of human PrDs, and the current concepts of molecular diagnosis. Also, the authors provide a critical summary of the diagnostic methods with regard to the molecular subtypes.
Expert opinion: In spite of a lack of specific tests to detect disease-associated PrP in body fluids, the constellation of clinical symptoms, detection of protein 14-3-3 in cerebrospinal fluid, electroencephalogram, cranial MRI and prion protein gene examinations, together have increased the specificity and sensitivity of in vivo diagnostics. As new forms of PrDs are reported, continuous evaluation of their incidence and the search for their etiology is crucial. Recent studies, suggesting prion-like properties of certain proteinopathies associated with Parkinson's or Alzheimer's disease, have again brought PrDs to the center of interest as a model of diseases with disordered protein processing.