- Author: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS; Chief Editor: Niranjan N Singh, MD, DM more...
The prion diseases are a large group of related neurodegenerative conditions, which affect both animals and humans. Included are Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker (GSS) in humans, bovine spongiform encephalopathy (BSE, or "mad cow disease") in cattle, chronic wasting disease (CWD) in mule deer and elk, and scrapie in sheep. These diseases all have long incubation periods but are typically rapidly progressive once clinical symptoms begin. All prion diseases are fatal, with no effective form of treatment currently; however, increased understanding of their pathogenesis has recently led to the promise of effective therapeutic interventions in the near future.
Prion diseases are unique in that they can be inherited, they can occur sporadically, or they can be infectious. The infectious agent in the prion disease is composed mainly or entirely of an abnormal conformation of a host-encoded glycoprotein called the prion protein. The replication of prions involves the recruitment of the normally expressed prion protein, which has mainly an alpha-helical structure, into a disease-specific conformation that is rich in beta-sheet.
The first of these diseases to be described was scrapie, a disease of sheep recognized for over 250 years. This illness, manifested by hyperexcitability, itching, and ataxia, leads to paralysis and death. It is called scrapie because of the tendency of affected animals to rub against the fences of their pens in order to stay upright, reflecting their cerebellar dysfunction. The transmission of this disease was demonstrated first in 1943 when a population of Scottish sheep was accidentally inoculated against a common virus using a formalin extract of lymphoid tissue from an animal with scrapie. Accidental transmission of prions is a recurrent event in the history of these agents and is related to their unusual biophysical properties.
For related information, see Medscape Reference article Variant Creutzfeldt-Jakob Disease and Bovine Spongiform Encephalopathy.
A unifying feature of all the prionoses is their neuropathology. These illnesses tend to affect the gray matter of the central nervous system (CNS), producing neuronal loss, gliosis, and characteristic spongiform change. The latter is a vacuolation of the neuropil, and to a variable degree, of the neurons, shown below.
In addition, plaques with the typical staining properties of amyloid (eg, apple-green birefringence after Congo Red staining when viewed under polarized light) are observed in many of these conditions. In approximately 10% of patients with CJD, amyloid is present in the cerebellum or in the cerebral hemispheres. All cases of GSS are associated with multicentric cerebellar plaques. These amyloid plaques are immunoreactive with antibodies to the prion protein and do not immunoreact with antibodies to other amyloidogenic proteins, such as the amyloid-beta (which is deposited in Alzheimer disease).
Etiology of PrP-related diseases
Highly divergent hypotheses have been put forward regarding the makeup of the prions, including that they consist of nucleic acid only or protein only, are lacking both protein and nucleic acid, or are a polysaccharide. The most widely accepted hypothesis, first described by Griffith and more explicitly detailed by Stanley Prusiner, MD, is the protein only hypothesis. Prusiner introduced the term prion to indicate that scrapie is related to a proteinaceous infectious particle (PrP).
This hypothesis was initially greeted with great skepticism in the scientific community; now it represents the current dogma, and Prusiner won the 1998 Noble Prize for Science. This hypothesis suggests that prions contain no nucleic acid and are referred to as PrPSc. The latter represents a conformationally modified form of a normal cellular PrPC, which is a normal host protein found on the surface of many cells, in particular neurons. PrPSc, when introduced into normal healthy cells, causes the conversion of PrPC into PrPSc, initiating a self-perpetuating vicious cycle.
Other hypotheses for prion have included the virino hypothesis. This hypothesis suggests that the infectious agent consists of a nucleic acid with host-derived PrPSc serving as a coat. The latter would explain the lack of an immunological and inflammatory response, while the presence of a nucleic acid provides an explanation for the numerous strains of scrapie, each with distinctive features. Other investigators have also suggested that the scrapie agent is a conventional virus with highly atypical properties. However, despite extensive searches, no nucleic acid associated with prion infection has been detected so far.
The protein-only hypothesis of prion propagation proposes the existence of an infectious agent composed solely of protein. Recent reports claim that apart from the rare prion diseases, prion-like transmission of altered proteins may occur in several human diseases of the brain and other organs.[8, 9, 10]
Cell biology of prions - Normal cellular function of PrP
The human PrP gene (PRNP) is found on chromosome 20 and encodes a protein of 253 amino acids. PrPC is a glycosylphosphatidylinositol-anchored cell-surface glycoprotein; some have speculated that it may have a role in cell adhesion or signaling processes, but its exact cellular function remains unknown. The N-terminal region of PrP contains a segment of 5 repeats of an 8–amino acid sequence (ie, octapeptide repeat region) that contains a high-affinity binding site for copper ions; hence, PrP may have a role in copper transport or metabolism. Recent evidence suggests that copper imbalance is an early change during prion infections. The function(s) of PrPC is likely to be of some importance because PrP is highly conserved among mammals and is found in all vertebrates.[12, 13] Also, prionlike proteins called PSI and URE3 are expressed in yeast.
PrP is found in most tissues of the body but is expressed at highest levels in the CNS, in particular in neurons. PrP is also expressed widely on cells of the immune system. PrP knockout mice, which are engineered not to express the PrP gene, show no obvious pathological phenotype. However, these mice have been shown to have abnormalities in synaptic physiology and in circadian rhythms and sleep.
The secondary structure of PrPC was first elucidated by nuclear magnetic resonance (NMR) imaging using recombinant mouse PrP protein. More recently, this has been achieved using recombinant hamster and human PrP.[19, 20, 21] These studies have shown that PrPC is about 40% alpha-helix and about 3% beta-sheet. No high-resolution structural studies, such as NMR imaging, have been performed on PrPSc because it is highly insoluble and aggregated, which are properties that prevent use of these techniques. However, less exact structural methods such as circular dichroism and Fourier transform infrared spectroscopy have shown PrPSc to contain about 45% beta-sheet and 30% alpha-helix.[22, 23] This high beta-sheet content correlates with PrPSc resistance to enzymatic digestion and infectivity.
Prion strains and the species barrier
Many lines of evidence support the protein only hypothesis of prion propagation; however, a difficulty is the existence of several distinct isolates or strains of prions that can be stably passaged among inbred mice of the same genotype. The existence of strains suggests that PrPSc could adopt multiple distinct pathological conformations. Strains are defined by the production of distinct patterns of incubation time, distributions of CNS involvement, and the pattern of proteolytic cleavage of PrPSc following proteinase K (PK) digestion.[5, 25] For example, at least 14 significantly different scrapie strains have been isolated from natural sheep scrapie by passage into mice.[24, 26]
The best studied are the two strains of transmissible mink encephalopathy (TME) called hyper (HY) and drowsy (DY).[27, 28] The truncated DY PrPSc fragments (PrP27-30) migrate 1-2 kd faster than similar preparations of HY because sites of PK cleavage differ and the two strains differ in terms of beta-sheet content.[28, 27]
Parchi et al defined 2 distinct types of sporadic CJD based on the analysis of PrP codon 129, which encodes either a valine or a methionine, and by the pattern of sodium dodecyl sulfate-polyacrylamide (SDS-PAGE) migration of the PrP27-30. Type 1 sporadic CJD has a molecular weight of the deglycosylated PrP27-30 of about 21 kd, while type 2 has a mobility of about 19 kd. Collinge et al reported 2 further types related to infectious CJD. These distinct types of sporadic CJD appear to have slightly different beta-sheet content that correlates with the degree of resistance to proteinase K digestion of each strain.
Each strain of prion has characteristic range of infectivity. For example the 263K strain is pathogenic for hamsters but does not infect mice. This effect is called a species barrier and is related to PrPSc being an effective template for homologous PrPC and a poor template for heterologous PrPC; hence, mouse PrPSc can effectively convert mouse PrPC, but it is a very poor template for human or hamster PrPC. This species barrier is not absolute, as is illustrated by the emergence of new variant CJD (vCJD).
The structure and folding properties of the cellular prion protein are well characterized, and, although its precise function remains enigmatic, constitutive knockout of protein expression in mice produces apparently healthy animals that are fully resistant to prion infection. In addition, data show that neuronal knockout of the gene encoding for prion protein during established brain infection leads to reversal of pathology and behavioral deficits.
How prions reach the CNS
Prion diseases are transmitted naturally by peripheral routes, either orally or transcutaneously; hence, how prions are able to reach the CNS is an important issue. Although the prion diseases are neurological conditions, critical events in their pathogenesis take place in restricted sites out of the nervous system, especially in peripheral lymphoid organs.
Lymphoid organs have long been known to be involved in the early stages of prion diseases.[34, 35, 36] In particular, the spleen and lymph nodes have been demonstrated to be the first sites of PrPSc replication after infection by peripheral routes, and they are also affected significantly following intracerebral challenge. Their importance for neuroinvasion after peripheral inoculation was suggested by studies showing that splenectomy and other methods that reduce peripheral lymphoid structures delay clinical manifestations.
The hematogenic spread of prions to the CNS is suggested by experiments that show BSE to be transmissible from sheep to sheep by blood transfusion. Three cases of vCJD infection associated with blood transfusion have also been observed (Health Protection Agency, Variant CJD and blood products). All received nonleucodepleted red blood cells.
The first case developed vCJD in 2003, 6.5 years following transfusion from a donor who developed vCJD 3.5 years following donation. The second patient died of causes unrelated to vCJD in 2004, 5 years following the transfusion. At autopsy, this individual had abnormal prion protein in the spleen and cervical lymph node but not in the brain, and other pathological features of vCJD were not observed. The donor developed symptoms of vCJD 18 months after his donation. The third patient developed vCJD in 2006, about 8 years following transfusion from a donor who was diagnosed with vCJD about 20 months after donation.
Hematogenic neuroinvasion has been shown to be dependent on the presence of B lymphocytes. However, because expression of the cellular prion protein by B cells is not required for neuroinvasion, some have suggested that their main function is to allow maintenance of follicular dendritic cells. However, more recent studies suggest that neuroinvasion is possible in the absence of both B cells and follicular dendritic cells. Other studies have implicated the distinct CD11c+ dendritic cell population in prion neuroinvasion.[22, 41]
In addition to hematogenous spread, prions can reach the brain via the parasympathetic vagus nerve. Hence, following intraperitoneal delivery of prions, disease can be delayed by sympathectomy or can be accelerated by sympathetic hyperinnervation of lymphoreticular organs.
Which of these two routes for neuroinvasion is most important remains unclear; it may be scrapie strain–dependent. However, a more complete understanding of these stages and the cells involved in prion spread from the periphery may allow for development of a pharmacological gatekeeper that can be used to stop the movement of infectivity.
The most common prion disease is CJD, with a uniform incidence of approximately 1 case per million population both in the United States and internationally. Familial forms of prion diseases, such as GSS and fatal familial insomnia (FFI), are much more rare. About 10% of cases of CJD are familial, with an autosomal dominant pattern of inheritance linked to mutations in the PRNP gene.
As of February 2006, 159 cases of definite or probable vCJD have been reported in the United Kingdom of which 153 persons have died (see The National Creutzfeldt-Jakob Disease Surveillance Unit). Whether these patients represent the beginning of a growing epidemic (such as that which occurred with BSE) or whether the number of cases will remain relatively low remains unclear. The first confirmed 3 cases were reported in 1995, with numbers of subsequent cases remaining relatively stable between 1996 and 2004 (9-28 cases per year). Only 5 cases were confirmed in 2005.
Two populations are disproportionally affected by CJD: Libyan-born Israelis and some populations in restricted areas of Slovakia where the incidence of CJD is 60-100 times greater than expected. These clusters were postulated to be related to dietary exposure of the scrapie agent; however, this was not supported by case-controlled studies. These local high rates of CJD are linked to a high prevalence of codon 200 mutations in the PRNP gene.
Prion-related diseases are relentlessly progressive and invariably lead to death.
The mean duration of sporadic CJD is 8 months.
vCJD has a slightly longer course, with a mean duration of 14 months.
Familial CJD has a mean duration of 26 months, while GSS has the longest course, about 60 months.
Sporadic CJD occurs throughout the world in people of all races and typically has similar features.
Some familial forms of prion disease, such as familial CJD, can have distinct features in an ethnic group. For example, familial CJD in the Libyan Jewish population associated with a codon 200 mutation has features of a peripheral neuropathy in addition to the more typical manifestations of CJD. [44, 45]
vCJD has been limited to Europe, with almost all cases occurring in the United Kingdom.
No sex preponderance is known in prion diseases, with some rare exceptions. For example, women had a greater tendency than men to develop kuru because it was part of the ritual cannibalism for women to eat the brains (and neural tissue has the highest dose of PrPSc).
See the list below:
The mean age of onset of sporadic CJD is 62 years. The incidence of sporadic CJD is about 1 case per million population; however, among individuals aged 60-74 years, the incidence is 5 cases per million population.  The age range can be broad; cases have been reported in people as young as 17 years and as old as 83 years. [47, 48]
vCJD occurs in younger patients, with a mean age of onset of 28 years.
Familial CJD, GSS, and FFI have mean ages of onset ranging from 45-49 years.
Sadowski M, Verma A, Wisniewski T. Prion Diseases. Bradley WG, Daroff RB, Fenichel GM, Jankovic J, eds. Neurology in Clinial Practice. Philadelphia: Elsevier Inc; 2004. 1613-1630.
Takada LT, Geschwind MD. Prion diseases. Semin Neurol. 2013 Sep. 33(4):348-56. [Medline].
Gordon WS. Advances in veterinary research. Vet Rec. 1946. 58:518-525.
Griffith JS, Hadlow WJ. Scrapie and kuru. Lancet. 1959. 11:289-290.
Prusiner SB, Scott MR, DeArmond SJ, Cohen FE. Prion protein biology. Cell. 1998 May 1. 93(3):337-48. [Medline].
Prusiner SB. Novel proteinaceous infectious particles cause scrapie. Science. 1982 Apr 9. 216(4542):136-44. [Medline].
Weissmann C. The Ninth Datta Lecture. Molecular biology of transmissible spongiform encephalopathies. FEBS Lett. 1996 Jun 24. 389(1):3-11. [Medline].
Clavaguera F, Bolmont T, Crowther RA, Abramowski D, Frank S, Probst A. Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol. 2009 Jul. 11(7):909-13. [Medline]. [Full Text].
Ren PH, Lauckner JE, Kachirskaia I, Heuser JE, Melki R, Kopito RR. Cytoplasmic penetration and persistent infection of mammalian cells by polyglutamine aggregates. Nat Cell Biol. 2009 Feb. 11(2):219-25. [Medline]. [Full Text].
Thackray AM, Knight R, Haswell SJ, Bujdoso R, Brown DR. Metal imbalance and compromised antioxidant function are early changes in prion disease. Biochem J. 2002 Feb 15. 362:253-8. [Medline].
Windl O, Dempster M, Estibeiro P, Lathe R. A candidate marsupial PrP gene reveals two domains conserved in mammalian PrP proteins. Gene. 1995 Jul 4. 159(2):181-6. [Medline].
Masison DC, Edskes HK, Maddelein ML, Taylor KL, Wickner RB. [URE3] and [PSI] are prions of yeast and evidence for new fungal prions. Curr Issues Mol Biol. 2000 Apr. 2(2):51-9. [Medline].
Büeler H, Aguzzi A, Sailer A, et al. Mice devoid of PrP are resistant to scrapie. Cell. 1993 Jul 2. 73(7):1339-47. [Medline].
Collinge J, Whittington MA, Sidle KC, et al. Prion protein is necessary for normal synaptic function. Nature. 1994 Jul 28. 370(6487):295-7. [Medline].
Tobler I, Gaus SE, Deboer T, et al. Altered circadian activity rhythms and sleep in mice devoid of prion protein. Nature. 1996 Apr 18. 380(6575):639-42. [Medline].
Riek R, Hornemann S, Wider G, Billeter M, Glockshuber R, Wuthrich K. NMR structure of the mouse prion protein domain PrP(121-321). Nature. 1996 Jul 11. 382(6587):180-2. [Medline].
Hosszu LL, Baxter NJ, Jackson GS, et al. Structural mobility of the human prion protein probed by backbone hydrogen exchange. Nat Struct Biol. 1999 Aug. 6(8):740-3. [Medline].
James TL, Liu H, Ulyanov NB, et al. Solution structure of a 142-residue recombinant prion protein corresponding to the infectious fragment of the scrapie isoform. Proc Natl Acad Sci U S A. 1997 Sep 16. 94(19):10086-91. [Medline]. [Full Text].
Knaus KJ, Morillas M, Swietnicki W, Malone M, Surewicz WK, Yee VC. Crystal structure of the human prion protein reveals a mechanism for oligomerization. Nat Struct Biol. 2001 Sep. 8(9):770-4. [Medline].
Aucouturier P, Geissmann F, Damotte D, et al. Infected splenic dendritic cells are sufficient for prion transmission to the CNS in mouse scrapie. J Clin Invest. 2001 Sep. 108(5):703-8. [Medline].
Pan KM, Baldwin M, Nguyen J, et al. Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins. Proc Natl Acad Sci U S A. 1993 Dec 1. 90(23):10962-6. [Medline]. [Full Text].
Baron T. Identification of inter-species transmission of prion strains. J Neuropathol Exp Neurol. 2002 May. 61(5):377-83. [Medline].
Kascsak RJ, Rubenstein R, Merz PA, et al. Immunological comparison of scrapie-associated fibrils isolated from animals infected with four different scrapie strains. J Virol. 1986 Sep. 59(3):676-83. [Medline]. [Full Text].
Carp RI, Rubenstein R. Diversity and significance of scrapie strains. Semin Virol. 1991. 2:203-13.
Caughey B, Raymond GJ, Bessen RA. Strain-dependent differences in beta-sheet conformations of abnormal prion protein. J Biol Chem. 1998 Nov 27. 273(48):32230-5. [Medline].
Parchi P, Castellani R, Capellari S, et al. Molecular basis of phenotypic variability in sporadic Creutzfeldt-Jakob disease. Ann Neurol. 1996 Jun. 39(6):767-78. [Medline].
Collinge J, Sidle KC, Meads J, Ironside J, Hill AF. Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD. Nature. 1996 Oct 24. 383(6602):685-90. [Medline].
Kimberlin RH, Walker CA. Evidence that the transmission of one source of scrapie agent to hamsters involves separation of agent strains from a mixture. J Gen Virol. 1978 Jun. 39(3):487-96. [Medline].
Nicoll AJ, Collinge J. Preventing prion pathogenicity by targeting the cellular prion protein. Infect Disord Drug Targets. 2009 Feb. 9(1):48-57. [Medline].
Aucouturier P, Carp RI, Carnaud C, Wisniewski T. Prion diseases and the immune system. Clin Immunol. 2000 Aug. 96(2):79-85. [Medline].
Eklund CM, Kennedy RC, Hadlow WJ. Pathogenesis of scrapie virus infection in the mouse. J Infect Dis. 1967 Feb. 117(1):15-22. [Medline].
Fraser H, Dickinson AG. Studies of the lymphoreticular system in the pathogenesis of scrapie: the role of spleen and thymus. J Comp Pathol. 1978 Oct. 88(4):563-73. [Medline].
Kimberlin RH, Walker CA. Pathogenesis of mouse scrapie: dynamics of agent replication in spleen, spinal cord and brain after infection by different routes. J Comp Pathol. 1979 Oct. 89(4):551-62. [Medline].
Houston F, Foster JD, Chong A, Hunter N, Bostock CJ. Transmission of BSE by blood transfusion in sheep. Lancet. 2000 Sep 16. 356(9234):999-1000. [Medline].
Klein MA, Frigg R, Flechsig E, et al. A crucial role for B cells in neuroinvasive scrapie. Nature. 1997 Dec 18-25. 390(6661):687-90. [Medline].
Montrasio F, Frigg R, Glatzel M, et al. Impaired prion replication in spleens of mice lacking functional follicular dendritic cells. Science. 2000 May 19. 288(5469):1257-9. [Medline].
Shlomchik MJ, Radebold K, Duclos N, Manuelidis L. Neuroinvasion by a Creutzfeldt-Jakob disease agent in the absence of B cells and follicular dendritic cells. Proc Natl Acad Sci U S A. 2001 Jul 31. 98(16):9289-94. [Medline]. [Full Text].
Harischandra DS, Kondru N, Martin DP, Kanthasamy A, Jin H, Anantharam V, et al. Role of proteolytic activation of protein kinase Cd in the pathogenesis of prion disease. Prion. 2014 Jan-Feb. 8(1):143-53. [Medline].
Beekes M, McBride PA, Baldauf E. Cerebral targeting indicates vagal spread of infection in hamsters fed with scrapie. J Gen Virol. 1998 Mar. 79 ( Pt 3):601-7. [Medline].
Glatzel M, Heppner FL, Albers KM, Aguzzi A. Sympathetic innervation of lymphoreticular organs is rate limiting for prion neuroinvasion. Neuron. 2001 Jul 19. 31(1):25-34. [Medline].
Meiner Z, Halimi M, Polakiewicz RD, Prusiner SB, Gabizon R. Presence of prion protein in peripheral tissues of Libyan Jews with Creutzfeldt-Jakob disease. Neurology. 1992 Jul. 42(7):1355-60. [Medline].
Neufeld MY, Josiphov J, Korczyn AD. Demyelinating peripheral neuropathy in Creutzfeldt-Jakob disease. Muscle Nerve. 1992 Nov. 15(11):1234-9. [Medline].
Holman RC, Khan AS, Belay ED, Schonberger LB. Creutzfeldt-Jakob disease in the United States, 1979-1994: using national mortality data to assess the possible occurrence of variant cases. Emerg Infect Dis. 1996 Oct-Dec. 2(4):333-7. [Medline]. [Full Text].
Masters CL, Harris JO, Gajdusek DC, Gibbs CJ Jr, Bernoulli C, Asher DM. Creutzfeldt-Jakob disease: patterns of worldwide occurrence and the significance of familial and sporadic clustering. Ann Neurol. 1979 Feb. 5(2):177-88. [Medline].
Cathala F, Baron H. Clinical Aspects of Creutzfeldt-Jakob Disease. Prusiner SB, McKinley MP, eds. Prions: novel infectious pathogens causing scrapie and Creutzfeldt-Jakob disease. New York, NY: Academic Press; 1987. 467-509.
Gajdusek DC, Zigas V. Degenerative disease of the central nervous system in New Guinea: the epidemic occurrence of "kuru" in the native population. N Engl J Med. 1957. 257:974-978.
Gajdusek DC, Zigas V. Clinical, pathological and epidemiological study of an acute progressive degenerative disease of the central nervous system among natives of the eastern highlands of New Guinea. Am J Med. 1959. 26:442-469.
Liberski PP, Sikorska B, Lindenbaum S, Goldfarb LG, McLean C, Hainfellner JA, et al. Kuru: Genes, Cannibals and Neuropathology. J Neuropathol Exp Neurol. 2012 Feb. 71(2):92-103. [Medline].
Gajdusek DC, Gibbs CJ, Alpers M. Experimental transmission of a Kuru-like syndrome to chimpanzees. Nature. 1966 Feb 19. 209(5025):794-6. [Medline].
Jacob A. Uber eigenaritge erkrankungen des zentral-nervensystems mit bemerkenswertem anatomischen befunde (spastische pseudosklerose-encephalomyelopathie mit disseminierten degenerationsherden). Z Gesamte Neurol Psychiatre. 1921. 64:147-228.
Hofmann J, Wolf H, Grassmann A, Arndt V, Graham J, Vorberg I. Creutzfeldt-Jakob disease and mad cows: lessons learnt from yeast cells. Swiss Med Wkly. 2012 Jan 24. 142:[Medline].
Chiofalo N, Fuentes A, Galvez S. Serial EEG findings in 27 cases of Creutzfeldt-Jakob disease. Arch Neurol. 1980 Mar. 37(3):143-5. [Medline].
Gerstmann J, Straussler E, Scheinker I. Über eine eigenartige hereditar-familiare Erkrankung des Zentralnervensystems zugleich ein Beitrag zür frage des vorzeitigen kokalen Alterns. Z Neurol. 1936. 154:736-762.
Ghetti B, Tagliavini F, Giaccone G, et al. Familial Gerstmann-Sträussler-Scheinker disease with neurofibrillary tangles. Mol Neurobiol. 1994 Feb. 8(1):41-8. [Medline].
Ghetti B, Piccardo P, Spillantini MG, et al. Vascular variant of prion protein cerebral amyloidosis with tau-positive neurofibrillary tangles: the phenotype of the stop codon 145 mutation in PRNP. Proc Natl Acad Sci U S A. 1996 Jan 23. 93(2):744-8. [Medline]. [Full Text].
Medori R, Tritschler HJ, LeBlanc A, et al. Fatal familial insomnia, a prion disease with a mutation at codon 178 of the prion protein gene. N Engl J Med. 1992 Feb 13. 326(7):444-9. [Medline].
Goldfarb LG, Brown P, Haltia M, et al. Creutzfeldt-Jakob disease cosegregates with the codon 178Asn PRNP mutation in families of European origin. Ann Neurol. 1992 Mar. 31(3):274-81. [Medline].
Solvason HB, Harris B, Zeifert P, Flores BH, Hayward C. Psychological versus biological clinical interpretation: a patient with prion disease. Am J Psychiatry. 2002 Apr. 159(4):528-37. [Medline].
Oliveros RG, Saracibar N, Gutierrez M, , Munon T, Gonzalez-Pinto A. Catatonia due to a prion familial disease. Schizophr Res. 2009 Mar. 108(1-3):309-10. [Medline].
Collinge J. Human prion diseases and bovine spongiform encephalopathy (BSE). Hum Mol Genet. 1997. 6(10):1699-705. [Medline].
Collinge J, Rossor M. A new variant of prion disease. Lancet. 1996 Apr 6. 347(9006):916-7. [Medline].
Bateman D, Hilton D, Love S, Zeidler M, Beck J, Collinge J. Sporadic Creutzfeldt-Jakob disease in a 18-year-old in the UK. Lancet. 1995 Oct 28. 346(8983):1155-6. [Medline].
Britton TC, al-Sarraj S, Shaw C, Campbell T, Collinge J. Sporadic Creutzfeldt-Jakob disease in a 16-year-old in the UK. Lancet. 1995 Oct 28. 346(8983):1155. [Medline].
Collee JG, Bradley R. BSE: a decade on--Part I. Lancet. 1997 Mar 1. 349(9052):636-41. [Medline].
Will RG. Surveillance of prion disease in humans. HF Baker, Ridley RM, eds. Methods in Molecular Medicine: Prion Diseases. Totowa, NJ: Humana Press Inc; 1996. 119-137.
Liberski PP, Guiroy DC, Williams ES, Walis A, Budka H. Deposition patterns of disease-associated prion protein in captive mule deer brains with chronic wasting disease. Acta Neuropathol. 2001 Nov. 102(5):496-500. [Medline].
Khan RM, Gunaratne LA, Kinmont JC. Rapid fracture healing in a patient with inherited prion disease. Ann R Coll Surg Engl. 2009 Apr. 91(3):261-2. [Medline].
Belay ED, Gambetti P, Schonberger LB, et al. Creutzfeldt-Jakob disease in unusually young patients who consumed venison. Arch Neurol. 2001 Oct. 58(10):1673-8. [Medline].
Raymond GJ, Bossers A, Raymond LD, et al. Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease. EMBO J. 2000 Sep 1. 19(17):4425-30. [Medline]. [Full Text].
Angers RC, Browning SR, Seward TS, et al. Prions in skeletal muscles of deer with chronic wasting disease. Science. 2006 Feb 24. 311(5764):1117. [Medline].
Marsh RF, Kincaid AE, Bessen RA, Bartz JC. Interspecies transmission of chronic wasting disease prions to squirrel monkeys (Saimiri sciureus). J Virol. 2005 Nov. 79(21):13794-6. [Medline].
Hamaguchi T, Noguchi-Shinohara M, Nozaki I, Nakamura Y, Sato T, Kitamoto T. Medical procedures and risk for sporadic Creutzfeldt-Jakob disease, Japan, 1999-2008. Emerg Infect Dis. 2009 Feb. 15(2):265-71. [Medline]. [Full Text].
Appleby BS, Rincon-Beardsley TD, Appleby KK, Crain BJ, Wallin MT. Initial diagnoses of patients ultimately diagnosed with prion disease. J Alzheimers Dis. 2014 Jan 1. 42(3):833-9. [Medline].
Seipelt M, Zerr I, Nau R, et al. Hashimoto's encephalitis as a differential diagnosis of Creutzfeldt-Jakob disease. J Neurol Neurosurg Psychiatry. 1999 Feb. 66(2):172-6. [Medline].
Castillo P, Woodruff B, Caselli R, et al. Steroid-responsive encephalopathy associated with autoimmune thyroiditis. Arch Neurol. 2006 Feb. 63(2):197-202. [Medline].
Cossu G, Melis M, Molari A, et al. Creutzfeldt-Jakob disease associated with high titer of antithyroid autoantibodies: case report and literature review. Neurol Sci. 2003 Oct. 24(3):138-40. [Medline].
Young GS, Geschwind MD, Fischbein NJ, et al. Diffusion-weighted and fluid-attenuated inversion recovery imaging in Creutzfeldt-Jakob disease: high sensitivity and specificity for diagnosis. AJNR Am J Neuroradiol. 2005 Jun-Jul. 26(6):1551-62. [Medline].
Rees HC, Maddison BC, Owen JP, Whitelam GC, Gough KC. Concentration of disease-associated prion protein with silicon dioxide. Mol Biotechnol. 2009 Mar. 41(3):254-62. [Medline].
Laude H. Beringue V. Newly discovered forms of prion diseases in ruminants. [Review]. Pathologie Biologie. 2009. 57(2):117-26.
Sim VL. Caughey B. Recent advances in prion chemotherapeutics. [Review]. Infectious Disorders - Drug Targets. 2009. 9(1):81-91.
Relano-Gines A. Gabelle A. Lehmann S. Milhavet O. Crozet C. Gene and cell therapy for prion diseases. [Review]. Infectious Disorders - Drug Targets. 2009. 9(1):58-68.
Caspi S, Halimi M, Yanai A, Sasson SB, Taraboulos A, Gabizon R. The anti-prion activity of Congo red. Putative mechanism. J Biol Chem. 1998 Feb 6. 273(6):3484-9. [Medline].
Demaimay R, Harper J, Gordon H, Weaver D, Chesebro B, Caughey B. Structural aspects of Congo red as an inhibitor of protease-resistant prion protein formation. J Neurochem. 1998 Dec. 71(6):2534-41. [Medline].
Doh-ura K, Ishikawa K, Murakami-Kubo I, et al. Treatment of transmissible spongiform encephalopathy by intraventricular drug infusion in animal models. J Virol. 2004 May. 78(10):4999-5006. [Medline]. [Full Text].
Demaimay R, Chesebro B, Caughey B. Inhibition of formation of protease-resistant prion protein by Trypan Blue, Sirius Red and other Congo Red analogs. Arch Virol Suppl. 2000. 277-83. [Medline].
Tagliavini F, McArthur RA, Canciani B, et al. Effectiveness of anthracycline against experimental prion disease in Syrian hamsters. Science. 1997 May 16. 276(5315):1119-22. [Medline].
Adjou KT, Demaimay R, Lasmezas CI, Seman M, Deslys JP, Dormont D. Differential effects of a new amphotericin B derivative, MS-8209, on mouse BSE and scrapie: implications for the mechanism of action of polyene antibiotics. Res Virol. 1996 Jul-Aug. 147(4):213-8. [Medline].
Adjou KT, Demaimay R, Deslys JP, et al. MS-8209, a water-soluble amphotericin B derivative, affects both scrapie agent replication and PrPres accumulation in Syrian hamster scrapie. J Gen Virol. 1999 Apr. 80 ( Pt 4):1079-85. [Medline].
Adjou KT, Privat N, Demart S, et al. MS-8209, an amphotericin B analogue, delays the appearance of spongiosis, astrogliosis and PrPres accumulation in the brain of scrapie-infected hamsters. J Comp Pathol. 2000 Jan. 122(1):3-8. [Medline].
Mange A, Milhavet O, McMahon HE, Casanova D, Lehmann S. Effect of amphotericin B on wild-type and mutated prion proteins in cultured cells: putative mechanism of action in transmissible spongiform encephalopathies. J Neurochem. 2000 Feb. 74(2):754-62. [Medline].
Mange A, Nishida N, Milhavet O, McMahon HE, Casanova D, Lehmann S. Amphotericin B inhibits the generation of the scrapie isoform of the prion protein in infected cultures. J Virol. 2000 Apr. 74(7):3135-40. [Medline].
Farquhar C, Dickinson A, Bruce M. Prophylactic potential of pentosan polysulphate in transmissible spongiform encephalopathies. Lancet. 1999 Jan 9. 353(9147):117. [Medline].
Ladogana A, Casaccia P, Ingrosso L, et al. Sulphate polyanions prolong the incubation period of scrapie-infected hamsters. J Gen Virol. 1992 Mar. 73 ( Pt 3):661-5. [Medline].
Farquhar CF, Dickinson AG. Prolongation of scrapie incubation period by an injection of dextran sulphate 500 within the month before or after infection. J Gen Virol. 1986 Mar. 67 ( Pt 3):463-73. [Medline].
Priola SA, Raines A, Caughey WS. Porphyrin and phthalocyanine antiscrapie compounds. Science. 2000 Feb 25. 287(5457):1503-6. [Medline].
Priola SA, Raines A, Caughey W. Prophylactic and therapeutic effects of phthalocyanine tetrasulfonate in scrapie-infected mice. J Infect Dis. 2003 Sep 1. 188(5):699-705. [Medline].
Masullo C, Macchi G, Xi YG, Pocchiari M. Failure to ameliorate Creutzfeldt-Jakob disease with amphotericin B therapy. J Infect Dis. 1992 Apr. 165(4):784-5. [Medline].
Korth C, May BC, Cohen FE, Prusiner SB. Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease. Proc Natl Acad Sci U S A. 2001 Aug 14. 98(17):9836-41. [Medline]. [Full Text].
Nakajima M, Yamada T, Kusuhara T, et al. Results of quinacrine administration to patients with Creutzfeldt-Jakob disease. Dement Geriatr Cogn Disord. 2004. 17(3):158-63. [Medline].
Barret A, Tagliavini F, Forloni G, et al. Evaluation of quinacrine treatment for prion diseases. J Virol. 2003 Aug. 77(15):8462-9. [Medline].
Collins SJ, Lewis V, Brazier M, Hill AF, Fletcher A, Masters CL. Quinacrine does not prolong survival in a murine Creutzfeldt-Jakob disease model. Ann Neurol. 2002 Oct. 52(4):503-6. [Medline].
Todd NV, Morrow J, Doh-ura K, et al. Cerebroventricular infusion of pentosan polysulphate in human variant Creutzfeldt-Jakob disease. J Infect. 2005 Jun. 50(5):394-6. [Medline].
Soto C, Kascsak RJ, Saborio GP, et al. Reversion of prion protein conformational changes by synthetic beta-sheet breaker peptides. Lancet. 2000 Jan 15. 355(9199):192-7. [Medline].
Wisniewski T, Aucouturier P, Soto C, Frangione B. The prionoses and other conformational disorders. Amyloid. 1998 Sep. 5(3):212-24. [Medline].
Wisniewski T, Sigurdsson EM, Aucouturier P, et al. Conformation as a therapeutic target in the prionoses and other neurodegenerative conditions. Molecular and Cellular Pathology in Prion Disease. 2001.
De Gioia L, Selvaggini C, Ghibaudi E, et al. Conformational polymorphism of the amyloidogenic and neurotoxic peptide homologous to residues 106-126 of the prion protein. J Biol Chem. 1994 Mar 18. 269(11):7859-62. [Medline].
Nguyen J, Baldwin MA, Cohen FE, Prusiner SB. Prion protein peptides induce alpha-helix to beta-sheet conformational transitions. Biochemistry. 1995 Apr 4. 34(13):4186-92. [Medline].
Zhang H, Kaneko K, Nguyen JT, et al. Conformational transitions in peptides containing two putative alpha-helices of the prion protein. J Mol Biol. 1995 Jul 21. 250(4):514-26. [Medline].
Naiki H, Higuchi K, Nakakuki K, Takeda T. Kinetic analysis of amyloid fibril polymerization in vitro. Lab Invest. 1991 Jul. 65(1):104-10. [Medline].
Wisniewski T, Castano EM, Golabek A, Vogel T, Frangione B. Acceleration of Alzheimer's fibril formation by apolipoprotein E in vitro. Am J Pathol. 1994 Nov. 145(5):1030-5. [Medline].
Sigurdsson EM, Permanne B, Soto C, Wisniewski T, Frangione B. In vivo reversal of amyloid-beta lesions in rat brain. J Neuropathol Exp Neurol. 2000 Jan. 59(1):11-7. [Medline].
Soto C, Sigurdsson EM, Morelli L, Kumar RA, Castano EM, Frangione B. Beta-sheet breaker peptides inhibit fibrillogenesis in a rat brain model of amyloidosis: implications for Alzheimer's therapy. Nat Med. 1998 Jul. 4(7):822-6. [Medline].
Vidal R, Ghiso J, Wisniewski T, Frangione B. Alzheimer's presenilin 1 gene expression in platelets and megakaryocytes. Identification of a novel splice variant. FEBS Lett. 1996 Sep 9. 393(1):19-23. [Medline].
Sigurdsson EM, Brown DR, Alim MA, Scholtzova H, Carp R, Meeker HC, et al. Copper chelation delays the onset of prion disease. J Biol Chem. 2003 Nov 21. 278(47):46199-202. [Medline].
Sigurdsson EM. Immunotherapy for conformational diseases. Curr Pharm Des. 2006. 12(20):2569-85. [Medline].
Schenk D, Barbour R, Dunn W, et al. Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature. 1999 Jul 8. 400(6740):173-7. [Medline].
Weiner HL, Lemere CA, Maron R, et al. Nasal administration of amyloid-beta peptide decreases cerebral amyloid burden in a mouse model of Alzheimer's disease. Ann Neurol. 2000 Oct. 48(4):567-79. [Medline].
Janus C, Pearson J, McLaurin J, et al. A beta peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease. Nature. 2000 Dec 21-28. 408(6815):979-82. [Medline].
Morgan D, Diamond DM, Gottschall PE, et al. Arendash GW Ab peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature. 2001. 408:982-985.
Bard F, Cannon C, Barbour R, et al. Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat Med. 2000 Aug. 6(8):916-9. [Medline].
Sigurdsson EM, Brown DR, Daniels M, et al. Immunization delays the onset of prion disease in mice. Am J Pathol. 2002 Jul. 161(1):13-7. [Medline].
Goni F, Knudsen E, Schreiber F, et al. Mucosal vaccination delays or prevents prion infection via an oral route. Neuroscience. 2005. 133(2):413-21. [Medline].
Pankiewicz J, Sadowski M, Kascsak R, et al. Therapeutic mechanisms of anti-prion antibodies in a tissue culture model of prion infection. Soc Neurosci Abst. 2005.
Sigurdsson EM, Sy MS, Li R, Scholtzova H, Kascsak RJ, Kascsak R, et al. Anti-prion antibodies for prophylaxis following prion exposure in mice. Neurosci Lett. 2003 Jan 23. 336(3):185-7. [Medline].
Manuelidis L. Vaccination with an attenuated Creutzfeldt-Jakob disease strain prevents expression of a virulent agent. Proc Natl Acad Sci U S A. 1998 Mar 3. 95(5):2520-5. [Medline].
White AR, Enever P, Tayebi M, et al. Monoclonal antibodies inhibit prion replication and delay the development of prion disease. Nature. 2003 Mar 6. 422(6927):80-3. [Medline].
Enari M, Flechsig E, Weissmann C. Scrapie prion protein accumulation by scrapie-infected neuroblastoma cells abrogated by exposure to a prion protein antibody. Proc Natl Acad Sci U S A. 2001 Jul 31. 98(16):9295-9. [Medline]. [Full Text].
Peretz D, Williamson RA, Kaneko K, et al. Antibodies inhibit prion propagation and clear cell cultures of prion infectivity. Nature. 2001 Aug 16. 412(6848):739-43. [Medline].
Souan L, Tal Y, Felling Y, Cohen IR, Taraboulos A, Mor F. Modulation of proteinase-K resistant prion protein by prion peptide immunization. Eur J Immunol. 2001 Aug. 31(8):2338-46. [Medline].
Sigurdsson EM, Scholtzova H, Mehta PD, Frangione B, Wisniewski T. Immunization with a nontoxic/nonfibrillar amyloid-beta homologous peptide reduces Alzheimer's disease-associated pathology in transgenic mice. Am J Pathol. 2001 Aug. 159(2):439-47. [Medline].
Sigurdsson EM, Knudsen E, Asuni A, Fitzer-Attas C, Sage D, Quartermain D, et al. An attenuated immune response is sufficient to enhance cognition in an Alzheimer's disease mouse model immunized with amyloid-beta derivatives. J Neurosci. 2004 Jul 14. 24(28):6277-82. [Medline].
Coste J. Prowse C. Eglin R. Fang C. Subgroup on TSE. A report on transmissible spongiform encephalopathies and transfusion safety. [Review]. Vox Sanguinis. 2009. 96(4):284-291.
Lefrere JJ, Hewitt P. From mad cows to sensible blood transfusion: the risk of prion transmission by labile blood components in the United Kingdom and in France. Transfusion. 2009 Apr. 49(4):797-812. [Medline].
Brown P, Wolff A, Gajdusek DC. A simple and effective method for inactivating virus infectivity in formalin-fixed tissue samples from patients with Creutzfeldt-Jakob disease. Neurology. 1990 Jun. 40(6):887-90. [Medline].
Ironside JW, Bell JE. The 'high-risk' neuropathological autopsy in AIDS and Creutzfeldt-Jakob disease: principles and practice. Neuropathol Appl Neurobiol. 1996 Oct. 22(5):388-93. [Medline].
Aucouturier P, Kascsak RJ, Frangione B, Wisniewski T. Biochemical and conformational variability of human prion strains in sporadic Creutzfeldt-Jakob disease. Neurosci Lett. 1999 Oct 15. 274(1):33-6. [Medline].
Brown P, Rau EH, Johnson BK, Bacote AE, Gibbs CJ Jr, Gajdusek DC. New studies on the heat resistance of hamster-adapted scrapie agent: threshold survival after ashing at 600 degrees C suggests an inorganic template of replication. Proc Natl Acad Sci U S A. 2000 Mar 28. 97(7):3418-21. [Medline].
Budka H, Aguzzi A, Brown P, et al. Tissue handling in suspected Creutzfeldt-Jakob disease (CJD) and other human spongiform encephalopathies (prion diseases). Brain Pathol. 1995 Jul. 5(3):319-22. [Medline].
Bueler H, Fischer M, Lang Y, et al. Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature. 1992 Apr 16. 356(6370):577-82. [Medline].
Castilla J, Saa P, Soto C. Detection of prions in blood. Nat Med. 2005 Sep. 11(9):982-5. [Medline].
Chang B, Cheng X, Pan T, et al. An ultra-sensitive assay for detecting prions in blood. Proc Natl Acad Sci (USA) in press. 2006.
Citron M, Vigo-Pelfrey C, Teplow DB, et al. Excessive production of amyloid beta-protein by peripheral cells of symptomatic and presymptomatic patients carrying the Swedish familial Alzheimer disease mutation. Proc Natl Acad Sci U S A. 1994 Dec 6. 91(25):11993-7. [Medline]. [Full Text].
Collinge J, Palmer MS, Dryden AJ. Genetic predisposition to iatrogenic Creutzfeldt-Jakob disease. Lancet. 1991 Jun 15. 337(8755):1441-2. [Medline].
Collins SJ, Lawson VA, Masters CL. Transmissible spongiform encephalopathies. Lancet. 2004 Jan 3. 363(9402):51-61. [Medline].
Dlouhy SR, Hsiao K, Farlow MR, et al. Linkage of the Indiana kindred of Gerstmann-Sträussler-Scheinker disease to the prion protein gene. Nat Genet. 1992 Apr. 1(1):64-7. [Medline].
Dominguez DI, De Strooper B, Annaert W. Secretases as therapeutic targets for the treatment of Alzheimer's disease. Amyloid. 2001 Jun. 8(2):124-42. [Medline].
Dropcho EJ. Update on paraneoplastic syndromes. Curr Opin Neurol. 2005 Jun. 18(3):331-6. [Medline].
Finkenstaedt M, Szudra A, Zerr I, et al. MR imaging of Creutzfeldt-Jakob disease. Radiology. 1996 Jun. 199(3):793-8. [Medline].
Foster PR. Prions and blood products. Ann Med. 2000 Oct. 32(7):501-13. [Medline].
Gabizon R, Rosenmann H, Meiner Z, et al. Mutation and polymorphism of the prion protein gene in Libyan Jews with Creutzfeldt-Jakob disease (CJD). Am J Hum Genet. 1993 Oct. 53(4):828-35. [Medline].
Goldfarb LG, Brown P, Goldgaber D, et al. Creutzfeldt-Jakob disease and kuru patients lack a mutation consistently found in the Gerstmann-Sträussler-Scheinker syndrome. Exp Neurol. 1990 Jun. 108(3):247-50. [Medline].
Goldfarb LG, Brown P, McCombie WR, et al. Transmissible familial Creutzfeldt-Jakob disease associated with five, seven, and eight extra octapeptide coding repeats in the PRNP gene. Proc Natl Acad Sci U S A. 1991 Dec 1. 88(23):10926-30. [Medline]. [Full Text].
Goldfarb LG, Haltia M, Brown P, et al. New mutation in scrapie amyloid precursor gene (at codon 178) in Finnish Creutzfeldt-Jakob kindred. Lancet. 1991 Feb 16. 337(8738):425. [Medline].
Goldfarb LG, Mitrova E, Brown P, Toh BK, Gajdusek DC. Mutation in codon 200 of scrapie amyloid protein gene in two clusters of Creutzfeldt-Jakob disease in Slovakia. Lancet. 1990 Aug 25. 336(8713):514-5. [Medline].
Goldfarb LG, Petersen RB, Tabaton M, et al. Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease phenotype determined by a DNA polymorphism. Science. 1992 Oct 30. 258(5083):806-8. [Medline].
Goldgaber D, Goldfarb LG, Brown P, et al. Mutations in familial Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker's syndrome. Exp Neurol. 1989 Nov. 106(2):204-6. [Medline].
Haass C, Hung AY, Schlossmacher MG, Teplow DB, Selkoe DJ. beta-Amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms. J Biol Chem. 1993 Feb 15. 268(5):3021-4. [Medline].
Head MW, Bunn TJ, Bishop MT, et al. Prion protein heterogeneity in sporadic but not variant Creutzfeldt-Jakob disease: UK cases 1991-2002. Ann Neurol. 2004 Jun. 55(6):851-9. [Medline].
Hetz C, Soto C. Protein misfolding and disease: the case of prion disorders. Cell Mol Life Sci. 2003 Jan. 60(1):133-43. [Medline].
Hill AF, Zeidler M, Ironside J, Collinge J. Diagnosis of new variant Creutzfeldt-Jakob disease by tonsil biopsy. Lancet. 1997 Jan 11. 349(9045):99-100. [Medline].
Hsiao K, Baker HF, Crow TJ, et al. Linkage of a prion protein missense variant to Gerstmann-Sträussler syndrome. Nature. 1989 Mar 23. 338(6213):342-5. [Medline].
Hsiao K, Dlouhy SR, Farlow MR, et al. Mutant prion proteins in Gerstmann-Sträussler-Scheinker disease with neurofibrillary tangles. Nat Genet. 1992 Apr. 1(1):68-71. [Medline].
Hsiao K, Doh-ura K, KitamotoT. A prion protein amino acid substitution in ataxic Gerstmann-Straussler syndrome. Ann Neurol. 1989. 26:137.
Hsiao K, Meiner Z, Kahana E, et al. Mutation of the prion protein in Libyan Jews with Creutzfeldt-Jakob disease. N Engl J Med. 1991 Apr 18. 324(16):1091-7. [Medline].
Jeong JK, Lee JH, Moon JH, Lee YJ, Park SY. Melatonin-mediated ß-catenin activation protects neuron cells against prion protein-induced neurotoxicity. J Pineal Res. 2014 Nov. 57(4):427-34. [Medline].
Kitamoto T, Ohta M, Doh-ura K, Hitoshi S, Terao Y, Tateishi J. Novel missense variants of prion protein in Creutzfeldt-Jakob disease or Gerstmann-Sträussler syndrome. Biochem Biophys Res Commun. 1993 Mar 15. 191(2):709-14. [Medline].
Kovacs GG, Voigtlander T, Gelpi E, Budka H. Rationale for diagnosing human prion disease. World J Biol Psychiatry. 2004 Apr. 5(2):83-91. [Medline].
Maness LM, Banks WA, Podlisny MB, Selkoe DJ, Kastin AJ. Passage of human amyloid beta-protein 1-40 across the murine blood-brain barrier. Life Sci. 1994. 55(21):1643-50. [Medline].
Miyazono M, Kitamoto T, Doh-ura K, Iwaki T, Tateishi J. Creutzfeldt-Jakob disease with codon 129 polymorphism (valine): a comparative study of patients with codon 102 point mutation or without mutations. Acta Neuropathol. 1992. 84(4):349-54. [Medline].
Nochlin D, Sumi SM, Bird TD, et al. Familial dementia with PrP-positive amyloid plaques: a variant of Gerstmann-Sträussler syndrome. Neurology. 1989 Jul. 39(7):910-8. [Medline].
Owen F, Poulter M, Lofthouse R, et al. Insertion in prion protein gene in familial Creutzfeldt-Jakob disease. Lancet. 1989 Jan 7. 1(8628):51-2. [Medline].
Owen F, Poulter M, Shah T, et al. An in-frame insertion in the prion protein gene in familial Creutzfeldt-Jakob disease. Brain Res Mol Brain Res. 1990 Apr. 7(3):273-6. [Medline].
Quadrio I, Ugnon-Cafe S, Dupin M, Esposito G, Streichenberger N, Krolak-Salmon P. Rapid diagnosis of human prion disease using streptomycin with tonsil and brain tissues. Lab Invest. 2009 Apr. 89(4):406-13. [Medline].
Ripoll L, Laplanche JL, Salzmann M, et al. A new point mutation in the prion protein gene at codon 210 in Creutzfeldt-Jakob disease. Neurology. 1993 Oct. 43(10):1934-8. [Medline].
Sakaguchi S. Prospects for preventative vaccines against prion diseases. Protein & Peptide Letters. 2009. 16(3):260-70.
Soto C, Saborio GP, Anderes L. Cyclic amplification of protein misfolding: application to prion-related disorders and beyond. Trends Neurosci. 2002 Aug. 25(8):390-4. [Medline].
Weissmann C. Molecular genetics of transmissible spongiform encephalopathies. J Biol Chem. 1999 Jan 1. 274(1):3-6. [Medline].
Will RG, Ironside JW, Zeidler M, et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet. 1996 Apr 6. 347(9006):921-5. [Medline].
|Sporadic CJD||Human||Spontaneous PrPC to PrPSc conversion or somatic mutation|
|Iatrogenic CJD||Human||Infection from prion-containing material, eg, dura mater, electrode|
|Familial CJD||Human||Mutations in the PrP gene|
|vCJD||Human||Infection from BSE|
|GSS||Human||Mutations in the PrP gene|
|FFI||Human||D178N mutation in the PrP gene, with M129 polymorphism|
|Sporadic fatal insomnia||Human||Spontaneous PrPC to PrPSc conversion or somatic mutation|
|Scrapie||Sheep||Infection in susceptible sheep|
|BSE||Cattle||Infection from contaminated food|
|TME||Mink||Infection from sheep or cattle in food|
|CWD||Mule, deer, elk||Unclear|
|Feline spongiform encephalopathy||Cats||Infection from contaminated food|
|Exotic ungulate encephalopathy||Nyala, oryx, kudu||Infection from contaminated food|
|Limbic encephalitis||Small cell lung carcinoma
|Anti-Hu, antiCV2,PCA-2, ANNA-3
Anti-Ma2 Anti-VGKC, anti-CV2
|Cerebellar degeneration||Breast, ovary, lung, others||Anti-Yo, anti-Ma, anti-Ri
|Opsoclonus myoclonus||Breast, ovarian, small cell carcinoma of lung
|Anti-Ri, anti-Yo, Anti-Hu,