This article presents an update on the clinical aspects of human prion disease, including the wide spectrum of their presentations.
Prion diseases, a group of disorders caused by abnormally shaped proteins called prions, occur in sporadic (Jakob-Creutzfeldt disease), genetic (genetic Jakob-Creutzfeldt disease, Gerstmann-Stra¨ussler-Scheinker syndrome, and fatal familial insomnia), and acquired (kuru, variant Jakob-Creutzfeldt disease, and iatrogenic Jakob-Creutzfeldt disease) forms. This article presents updated information on the clinical features and diagnostic methods for human prion diseases. New antemortem potential diagnostic tests based on amplifying prions in order to detect them are showing very high specificity. Understanding of the diversity of possible presentations of human prion diseases continues to evolve, with some genetic forms progressing slowly over decades, beginning with dysautonomia and neuropathy and progressing to a frontal-executive dementia with pathology of combined prionopathy and tauopathy. Unfortunately, to date, all human prion disease clinical trials have failed to show survival benefit. A very rare polymorphism in the prion protein gene recently has been identified that appears to protect against prion disease; this finding, in addition to providing greater understanding of the prionlike mechanisms of neurodegenerative disorders, might lead to potential treatments.
Sporadic Jakob-Creutzfeldt disease is the most common form of human prion disease. Genetic prion diseases, resulting from mutations in the prion-related protein gene (PRNP), are classified based on the mutation, clinical phenotype, and neuropathologic features and can be difficult to diagnose because of their varied presentations. Perhaps most relevant to this Continuum issue on neuroinfectious diseases, acquired prion diseases are caused by accidental transmission to humans, but fortunately, they are the least common form and are becoming rarer as awareness of transmission risk has led to implementation of measures to prevent such occurrences.
Address correspondence to Dr Michael D. Geschwind, University of California San Francisco Memory and Aging Center, Box 1207, San Francisco, CA 94143-1207, firstname.lastname@example.org.
Relationship Disclosure: Dr Geschwind serves on the board of directors for San Francisco Bay Area Physicians for Social Responsibility, on the editorial board of Dementia & Neuropsychologia, and as a consultant for Best Doctors, Inc; the Gerson Lehrman Group, Inc; Guidepoint Global, LLC; Lewis Brisbois Bisgaard & Smith LLP; Lundbeck; MEDACorp; NeuroPhage Pharmaceuticals; and Quest Diagnostics. He receives research support from CurePSP, the Michael J. Homer Family Fund, the National Institute on Aging (R01 AG AG031189), Quest Diagnostics, and the Tau Consortium.
Unlabeled Use of Products/Investigational Use Disclosure: Dr Geschwind reports no disclosure.