Sporadic Human Prion Diseases

The sCJDMMl/sCJDMVl subtype displays either MM or MV at PrP codon 129 and type 1 PrP 5 It is the most common subtype and accounts for 60-70% of all sporadic human prion disease. This sCJD subtype has a mean age at clinical onset of 65 years of age and the mean duration of clinical symptoms prior to death is approximately four months. The symptoms at clinical presentation can include cognitive impairment, widened gait or ataxia, behavioral signs (including depression, anxiety. 

The sCJDW2 subtype has a VV at PrP codon 129 and type 2 PrP It is the second most common form of sCJD and accounts for -16% of all sporadic human prion disease. The mean age at onset is 60 years and the mean duration of the clinical phase is six months. Ataxia is the most common presenting symptom for this subtype. At later stages, dementia almost always develops and is accompanied by myoclonus and pyramidal signs. PSW on EEG is rare and CSE 14-3-3 is positive in -80% of cases. 

The SCJDMV2 subtype has MV at PrP codon 129 and type 2 PrP and it represents -9% of the sporadic cases. This sub-type has a phenotype very similar to that of sCJDVV2 except for a longer clinical phase before death (mean of 17 months), greater involvement of cognitive and mental symptoms at earlier stages, and frequent aphasia and apraxia at later stages. 

The SCJDMM2 subtype has MM at PrP codon 129 and type 2 PrP , and it accounts for 2-8% of the sporadic cases. The mean age at onset is 65 years and the mean clinical duration is 16 months. Cognitive impairment is the universal presenting symptom and is sometimes accompanied by aphasia. At later stages, myoclonus and pyramidal signs, and sometimes Parkinsonism, apraxia, and seizures, develop. There is no PSW on EEG while CSE 14-3-3 is positive in most cases. 

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The immune system plays a central role in the pathogenesis of prion infection. In the acquired human prion diseases, it is the initial site of agent replication prior to entry into the nervous system but the immune system does not appear to be essential in the pathogenesis of the familial and sporadic human prion diseases. Followdng peripheral exposure to the prion agent, the immune system can amplify prion infection but, interestingly, the adaptive immune response does not play a role in the clearance of the prion agent. 

Genetic Susceptibility to Acquired and Sporadic Human Prion Disease... 

With the discovery of ruminant prion diseases that resemble sporadic human prion disease, a certain element of balance in the epidemiology of prion disease could be established. However, the logic of this could also be reversed, and an important question could be raised might the low level occurrence of spontaneous farm animal prion disease underlie one or more forms of human prion disease, which are currently misinterpreted as spontaneous This major epidemiological and public-health issue will be the focus of discussion in this chapter. 

Gambetti P, Cali I, Notari S et al (2011) Molecular biology and pathology of prion strains in sporadic human prion diseases. Acta Neuropathol 121 79-90... 

Human prion disease most commonly presents with a sporadic etiology 793... 

Human prion diseases encompass the three etiological types of prion disease inherited, sporadic and acquired forms. 

Fig. 3. Classification of human prion diseases. Sporadic the transformation from PrPc (circle) to PrPSc (square) occurs without apparent cause. Familial a point mutation ( ) is thought to facilitate the transformation. Infectious the transformation arises via PrPSc which acts as a template. The kinetic equations are defined by Eigen (1996). The infectious form includes kuru, iatrogenic CJD (iCJD), variant CJD (vCJD first reported in 1996), bovine spongiform encephalopathy (BSE first reported in 1985), and scrapie. In the nucleation-dependent model, monomeric PrPc and PrPSc are in chemical equilibrium.

Further evidence supporting Hectd2 as a candidate gene was provided in an association study of HECTD2 SNPs in human prion diseases [68]. From the UK, patients with variant CJD and sporadic CJD were genotyped and compared to a control population. From PNG, kuru patients were genotyped and compared to... 

Known human prion diseases are Creutzfeldt-Jacob disease (CJD), Gerstmann-Straussler-Schienker syndrome (GSS) and fatal familial insomnia (FFI). GSS and FFI are inherited, whereas CJD may be inherited, sporadic or infectious. Another infectious form of CJD (iatrogenic CJD) arises from inadequately sterilized surgical instruments, dura mater grafts, and from human growth hormone isolated from cadavers. Kuru is a classical example of an infectious human prion disease transmitted by the ritual cannibalism of human brains, this disease was formerly common in the Fore tribe of New Guinea. 

Creutzfeldt-Jakob disease (CJD) the most common prion disease of humans and can have a sporadic, familial or acquired etiology. 

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