Prion Diseases

Abstract

Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are transmissible degenerative disorders of the central nervous system in mammals. TSEs are fatal and are caused by the proteinaceous infectious particles, termed prions that lack informational nucleic acids. TSEs include Creutzfeldt–Jakob disease in humans, scrapie in sheep, bovine spongiform encephalopathy or ‘mad cow disease’ in cattle and chronic wasting disease in deer and elk. These diseases manifest spongiform degeneration, reactive gliosis, and deposition of prion aggregates in the brain. The aetiology of TSEs is sporadic, genetic, or acquired. The primary structure of PrPC, conformational diversity of PrPSc, and their interplay influence intra‐ and inter‐species prion transmission. The role of lymphoreticular system is pivotal in early prion pathogenesis and neuroinvasion, whereas neuronal damage caused by prion infection could be achieved by several different mechanisms. Despite the potential risk for public health, diagnosis and therapy for prion diseases are currently unavailable.

Key Concepts:

  • Prion diseases represent a group of human and animal diseases that include sporadic, inherited, and acquired Creutzfeldt–Jakob disease (CJD), Gerstmann–Sträussler–Scheinker syndrome (GSS), and fatal familial insomnia (FFI) in humans, bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep, chronic wasting disease (CWD) in cervids, transmissible mink encephalopathy (TME) in mink, feline spongiform encephalopathy (FSE) in cats, and exotic ungluate encephalopathy (EUE) in exotic ungulates.

  • Prion diseases are fatal neurological disorders and caused by the unconventional proteinaceous pathogen, termed prion.

  • Prion diseases manifest characteristic clinical and neuropathological features.

  • Prion diseases are transmissible within and between the species.

  • Transmission of prion diseases is determined by the amino acid sequence variability of PrPC and prion strains conferred by conformational diversity of PrPSc.

  • The lymphoreticular system is crucial in prion pathogenesis and neuroinvasion.

  • Gain of pathologic PrPSc function and/or loss of neuroprotective PrPC function facilitate neuronal damages in the central nervous system by direct or indirect mechanism associated with astrocyte and microglial cells.

  • Atypical TSEs and human‐to‐human transmission of vCJD have been identified.

  • Diagnosis and therapy for prion disease are not available.

Keywords: prion; PrPSc; PrPC; TSE; CJD; Scrapie; BSE; CWD; TME; atypical TSE

Figure 1.

Characteristic neuropathological features of transmissible spongiform encephalopathies. (a) Haematoxylin and eosin (H&E) staining of the cerebral cortex of a patient with Creutzfeldt–Jakob disease displaying the characteristic spongiform, vacuole‐like morphology. (b) H&E staining of the cerebral cortex of a healthy individual. Provided by P. Nelson (University of Kentucky). (c) Activation and proliferation of reactive, swollen astrocytes is visualised in the grey matter of the brain of a patient with Creutzfeldt–Jakob disease by staining with antibodies against glial fibrillary acidic protein (brown colour). (d) Immunohistochemical staining of the gray matter of the brain of a patient with Creutzfeldt–Jakob disease using anti‐PrP antibodies representing prion protein deposits (brown colour). (e, f) Florid plaques in the cerebral cortex of a patient with variant Creutzfeldt–Jakob disease detected by H&E staining (e) and immunohistochemistry (f). I. Cali, W. Zou, and P. Gambetti (National Prion Disease Pathology Surveillance Center, Case Western Reserve University) provided the immunohistochemical image in panel (f).

Figure 2.

Possible models for prion neuroinvasion. In (a), B lymphocytes, which may be genotypically PrP‐positive or PrP‐negative, physically transport prions to their sites of replication in the spleen. These sites may be represented, in part or entirely, by follicular dendritic cells (FDCs). Direct neuroinvasion then occurs preferentially along fibres of the peripheral nervous system (PNS), which may support the transfer of prions to the central nervous system (CNS), depending on their own expression of PrPC. In (b) a second possibility is illustrated: B cells are not directly involved in neuroinvasion. In this instance, the crucial role of B cells in neuroinvasive scrapie relies on their function in inducing maturation of FDCs.

Figure 3.

BSE and vCJD cases. (a) BSE cases reported in the United Kingdom. (b) BSE cases worldwide excluding the United Kingdom. (c) vCJD cases reported in the United Kingdom. (d) Cumulative vCJD cases in individual countries. Statistical data were obtained from the World Organisation for Animal Health (OIE, www.oie.int) for BSE and National CJD Surveillance Unit for the United Kingdom (www.cjd.ed.ad.uk) for vCJD. The data of 2010 represent the number of BSE and vCJD cases as of September 2010 and June 2010, respectively. According to the U.S. case report, the third patient of the U.S. was born and raised in Saudi Arabia and has lived permanently in the U.S. since late 2005. The patient was most likely infected as a child when living in Saudi Arabia. The patient from Japan had resided in the UK during the period 1980–1996.

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Ryou, Chongsuk(May 2011) Prion Diseases. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000428.pub2]