Background: Transmissible spongiform encephalopathy (TSE) diseases are known to be zoonotic diseases that can infect different kinds of animals. The transmissibility of TSE, like that of other infectious diseases, shows marked species barrier, either being unable to infect heterologous species or difficult to form transmission experimentally. The similarity of the amino acid sequences of PrP among species is believed to be one of the elements in controlling the transmission TSE interspecies. Other factors, such as prion strains and host's microenvironment, may also participate in the process. Methods: Two mouse-adapted strains 139A and ME7 were cerebrally inoculated to Golden hamsters. Presences of scrapie associate fibril (SAF) and PrP^Sc in brains of the infected animals were tested by TEM assays and Western blots dynamically during the incubation periods. The pathogenic features of the novel prions in hamsters, including electrophoretic patterns, glycosylating profiles, immunoreactivities, proteinase K-resistances and conformational stabilities were comparatively evaluated. TSE-related neuropathological changes were assayed by histological examinations. Results: After long incubation times, mouse-adapted agents 139A and ME7 induced experimental scrapie in hamsters, respectively, showing obvious spongiform degeneration and PrP^Sc deposits in brains, especially in cortex regions. SAF and PrP^Sc in brains were observed much earlier than the onset of clinical symptoms. The molecular characteristics of the newly-formed PrP^Sc in hamsters, 139A-ha and ME7-ha, were obviously distinct from the original mouse agents, however, greatly similar as that of a hamster-adapted scrapie strain 263 K. Although the incubation times and main disease signs of the hamsters of 139A-ha and ME7-ha were different, the pathogenic characteristics and neuropathological changes were highly similar. Conclusions: This finding concludes that mouse-adapted agents 139A and ME7 change their pathogenic characteristics during the transmission to hamsters. The novel prions in hamsters' brains obtain new molecular properties with hamster-specificity.

Background Microglial activations have been described in different subtypes of human prion diseases such as sporadic Creutzfeldt-Jakob disease (CJD), variant CJD, Kuru and Gerstmann-Sträussler-Scheinker disease (GSS). However, the situation of microglia in other genetic prion diseases such as fatal familial insomnia (FFI) and familial CJD remains less understood. The brain microglia was evaluated comparatively between the FFI, G114V and sCJD cases in the study. Methods Specific Western blots, immunohistochemical and immunofluorescent assays were used to detect the changes of microglia and ELISA tests were used for levels of inflammatory cytokines. Results Western blots, immunohistochemical and immunofluorescent assays illustrated almost unchanged microglia in the temporal lobes of FFI and G114V gCJD, but obviously increased in those of sCJD. The Iba1-levels maintained comparable in six different brain regions of FFI and G114V cases, including thalamus, cingulate gyrus, frontal cortex, parietal cortex, occipital cortex and temporal cortex. ELISA tests for inflammatory cytokines revealed significantly up-regulated IL-1β, IL-6 and TNF-α in the brain homogenates from sCJD, but not in those from FFI and G114V gCJD. Conclusion Data here demonstrates silent brain microglia in FFI and G114V gCJD but obviously increased in sCJD, which reflects various pathogenesis of different human prion diseases subtypes.

Introduction: Transmissible spongiform encephalopathies are a group of neurodegenerative diseases of humans and animals. Genetic Creutzfeldt-Jakob diseases, in which mutations in the PRNP gene predispose to disease by causing the expression of abnormal PrP protein, include familial Creutzfeldt-Jakob disease, Gerstmann-Straussler-Scheinker syndrome and fatal familial insomnia. Case presentation: A 47-year-old Han-Chinese woman was hospitalized with a 2-year history of progressive dementia, tiredness, lethargy and mild difficulty in falling asleep. On neurological examination, there was severe apathy, spontaneous myoclonus of the lower limbs, generalized hyperreflexia and bilateral Babinski signs. A missense mutation (T to G) was identified at the position of nt 341 in one PRNP allele, leading to a change from glycine (Gly) to valine (Val) at codon 114. PK-resistant PrP^Sc was detected in brain tissues by Western blotting and immunohistochemical assays. Information on pedigree was collected notably by interviews with family members. A further four suspected patients in five consecutive generations of the family have been identified. One of them was hospitalized for progressive memory impairment at the age of 32. On examination, he had impairment of memory, calculation and comprehension, mild ataxia of the limbs, tremor and a left Babinski sign. He is still alive. Conclusion: This family with G114V inherited prion disease is the first to be described in China and represents the second family worldwide in which this mutation has been identified. Three other suspected cases have been retrospectively identified in this family, and a further case with suggestive clinical manifestations has been shown by gene sequencing to have the causal mutation.

Background: Human transmissible spongiform encephalopathies (HTSE), or Creutzfeldt-Jakob disease (CJD), is a group of rare and fatal diseases in central nervous system. Since outbreak of bovine spongiform encephalopathy (BSE) and variant CJD, a worldwide CJD surveillance network has been established under the proposition of WHO. In China, a national CJD surveillance system has started since 2002. The data of CJD surveillance from 2006 to 2007 was analyzed. Methods: Total 12 provinces are included in CJD surveillance system. The surveillance unit in each province consists of one or two sentinel hospitals and the provincial CDC. All suspected CJD cases reported from CJD surveillance were diagnosed and subtyped based on the diagnostic criteria for CJD issued by WHO. Results: Total 192 suspected CJD cases were reported and 5 genetic CJD, 51 probable and 30 possible sporadic CJD (sCJD) cases were diagnosed. The collected sCJD cases distribute sporadically without geographical clustering and seasonal relativity and the highest incidences in both probable and possible sCJD cases appeared in the group of 60–69 year. The most common three foremost symptoms were progressive dementia, cerebellum and mental-related symptoms. The probable sCJD patients owning both typical EEG alteration and CSF protein 14-3-3 positive have more characteristic clinical syndromes than the ones having only one positive. The polymorphisms of codon 129 of all tested reported cases shows typical patterns of Han Chinese as previous reports, that M129M are predominant whereas M129V are seldom. Conclusion: Chinese CJD patients possessed similar epidemiological and clinical characteristics as worldwide.

Genetic Creutzfeldt-Jakob disease (gCJD) with E200K mutation is one of the common subtypes of human genetic prion diseases worldwide. In this study, we systematically analyzed 30 Chinese E200K gCJD cases for their epidemiological, clinical, laboratory and genetic features. The patients came from 12 different provinces, majority in northern part of China. The onset age varied from 42 to 71 year-old (y), with the median of was 57 y. The CYP4X1 gene rs9793471 SNP was tested. Only one patient’s rs9793471 genotype was GA and the others’ were AA. The gender ratio (M: F) was 1:1.73 (11:19). The foremost symptoms and clinical progression of Chinese E200K gCJD patients were quite similar as sporadic CJD cases. Only a few cases (4/30) recalled clearly disease related family history. 74.1% (20/27), 86.7% (26/30) and 50.0% (13/26) of the cases were CSF 14-3-3 positive, sCJD associated abnormalities on MRI and special PSWC on EEG, respectively. The median clinical duration was 9 months (varying from 2 to 26 months). All 30 Chinese E200K gCJD patients were M129M and E219E homozygous. 21 members from 3 families conducted PRNP sequencing and 16 asymptomatic carriers of E200K mutation with M129M and E219E homozygous were identified. This is the largest study on E200K gCJD patients in China, which would benefit to the knowledge of E200K gCJD.