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Several human degenerative diseases appear as a result of the misfolding and aggregation of proteins.1 The prototype central nervous system proteinopathy is Creutzfeldt-Jakob disease (CJD), in which neuronal prion protein (PrP) with high α-helical content switches into a stable structure rich in β-pleated sheets in a self-catalyzing process that eventually, after a prolonged build-up phase, turns neurotoxic, causing a plethora of neurological and psychiatric symptoms.2 Although human prion diseases are rare, affecting around 1 to 2 people per million individuals each year,3 they are frequent differential diagnoses when patients present with clinical signs of rapidly progressive central nervous system disease. Reliable tools for diagnosis are needed because prion diseases are transmissible, which became clear in the 1930s when healthy sheep were inoculated with brain tissue from sheep affected by scrapie (a sheep prion disease) and fell ill following an incubation period of a few years.4 The transmissibility was further emphasized during the 1980s epidemic of bovine spongiform encephalopathy, a prion disease of cattle in the United Kingdom,5 which eventually also made it clear that bovine spongiform encephalopathy could be transmitted to humans in the form of variant CJD, typically affecting younger individuals showing prion aggregation in peripheral tissues as well as in the central nervous system.6-8 Clinical, epidemiological, and experimental research has demonstrated that prions are transmissible by multiple routes, may have long incubation periods, and are resistant to conditions that would inactivate most previously recognized pathogens, such as formalin treatment and heat denaturation.
Zetterberg H. Cerebrospinal Fluid Total Prion Protein: A Potential In Vivo Marker of Cerebral Prion Pathology. JAMA Neurol. 2015;72(3):261–263. doi:10.1001/jamaneurol.2014.4078
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