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Creutzfeldt–Jakob disease and other prion diseases

Nature Reviews Disease Primers volume 10, Article number: 14 (2024) Cite this article

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Abstract

Prion diseases share common clinical and pathological characteristics such as spongiform neuronal degeneration and deposition of an abnormal form of a host-derived protein, termed prion protein. The characteristic features of prion diseases are long incubation times, short clinical courses, extreme resistance of the transmissible agent to degradation and lack of nucleic acid involvement. Sporadic and genetic forms of prion diseases occur worldwide, of which genetic forms are associated with mutations in PRNP. Human to human transmission of these diseases has occurred due to iatrogenic exposure, and zoonotic forms of prion diseases are linked to bovine disease. Significant progress has been made in the diagnosis of these disorders. Clinical tools for diagnosis comprise brain imaging and cerebrospinal fluid tests. Aggregation assays for detection of the abnormally folded prion protein have a clear potential to diagnose the disease in peripherally accessible biofluids. After decades of therapeutic nihilism, new treatment strategies and clinical trials are on the horizon. Although prion diseases are relatively rare disorders, understanding their pathogenesis and mechanisms of prion protein misfolding has significantly enhanced the field in research of neurodegenerative diseases.

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Fig. 1: Crude mortality rates for sporadic Creutzfeldt–Jakob disease, 2018–2022.
Fig. 2: Epidemic curve for variant Creutzfeldt–Jakob disease.
Fig. 3: Mechanisms of prion disease pathogenesis.
Fig. 4: MRI lesion profile in sporadic Creutzfeldt-Jakob disease.
Fig. 5: Biological basis of therapeutic strategies in prion disease.

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Authors and Affiliations

  1. National Reference Center for CJD Surveillance, Department of Neurology, University Medical Center, Georg August University, Göttingen, Germany

    Inga Zerr & Peter Hermann

  2. Department of Neuroscience, Istituto Superiore di Sanità, Rome, Italy

    Anna Ladogana

  3. MRC Prion Unit at UCL, Institute of Prion Diseases, London, UK

    Simon Mead

  4. Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy

    Gianluigi Forloni

  5. Departments of Neurology, Psychiatry and Pathology, Case Western Reserve University, Cleveland, OH, USA

    Brian S. Appleby

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Contributions

Introduction (I.Z.); Epidemiology (A.L.); Mechanisms/pathophysiology (S.M.); Diagnosis, screening and prevention (P.H. and I.Z.); Management (G.F.); Quality of life (B.S.A.); Outlook (I.Z.); overview of Primer (I.Z.).

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Correspondence to Inga Zerr.

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Competing interests

I.Z. declares funding from BMG through the Robert Koch Institute, CJD Foundation and JPND; and consulting for IONIS, Sangamo, Gate Bio, Biogen and Lilly. B.S.A. declares funding from CDC, NIH, CJD Foundation, Ionis and Alector; consulting for Ionis, Sangamo, Gate Bio and Merck; and royalties from Wolters Kluwer. All other authors declare no competing interests.

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Nature Reviews Disease Primers thanks O. Andréoletti, H. Budka, G. Legname, P. Liberski and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Zerr, I., Ladogana, A., Mead, S. et al. Creutzfeldt–Jakob disease and other prion diseases. Nat Rev Dis Primers 10, 14 (2024). https://doi.org/10.1038/s41572-024-00497-y

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