Predicting susceptibility and incubation time of human-to-human transmission of vCJD

Bishop, Matthew; Hart, Patricia; Aitchison, L; Baybutt, Herbert; Plinston, Chris; Thomson, Val; Tuzi, Nadia L.; Head, Mark W.; Ironside, James W.; Will, Robert; Manson, Jean

doi:10.1016/s1474-4422(06)70413-6

Cited by 265 publications

(301 citation statements)

References 30 publications

Supporting

Mentioning

277

Contrasting

Unclassified

Order By: Relevance

“…We had expected that Ki-Hu129V/V were highly resistant to vCJD infection because these mice showed negative results when intraperitoneally challenged with vCJD prions (17,29). In addition, Bishop et al (15) reported a very low attack rate (1/16 (6.25%)) in humanized knock-in mice with the 129V/V genotype intracerebrally inoculated with vCJD prions. However, Ki-Hu129V/V showed moderate susceptibility to intracerebral transmission of vCJD in the present study (the sum total attack rate from two independent experiments using different inocula: 5/12 (41.7%)).…”

Section: Discussionmentioning

confidence: 99%

“…To gain insights into clinicopathological phenotype of vCJD with a PRNP genotype other than 129M/M, transmission studies using humanized transgenic mice or knock-in mice have been performed (11)(12)(13)(14)(15). These studies raised the possibility that the neuropathological phenotypes of vCJD in individuals with a 129M/V or 129V/V genotype might be different from that of patients with the 129M/M genotype and questioned the current neuropathological diagnostic criteria for vCJD.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Characterization of Variant Creutzfeldt-Jakob Disease Prions in Prion Protein-humanized Mice Carrying Distinct Codon 129 Genotypes

Takeuchi

Kobayashi

Ironside

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Secondary vCJD infection may occur in all human PRNP genotypes, but its clinicopathological and biochemical phenotype is uncertain. Results: The biochemical characteristics and transmission properties of the newly generated vCJD prions are not affected by the host PRNP genotypes. Conclusion: Secondary vCJD infection can be adequately diagnosed by biochemical analysis and experimental transmission. Significance: Effective means to identify secondary vCJD infection are presented.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Characterization of Variant Creutzfeldt-Jakob Disease Prions in Prion Protein-humanized Mice Carrying Distinct Codon 129 Genotypes

Takeuchi

Kobayashi

Ironside

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Inbred PrP knockout mice (129OlaPrP Ϫ/Ϫ ) and 129Ola wild-type mice (34), and mice whose endogenous PrP gene had been replaced with the human PrP gene with MM or VV 129 genotypes (28), were analyzed at 4 weeks of age. Mice infected with scrapie strains 79A and 87V along with their respective agematched controls were killed by cervical dislocation at 146 and 350 days, respectively, and the brains were immediately removed, rinsed in PBS, frozen in liquid nitrogen, and stored at Ϫ80°C before A␤ analysis.…”

Section: Methodsmentioning

confidence: 99%

Cellular prion protein regulates β-secretase cleavage of the Alzheimer's amyloid precursor protein

Parkin

Watt²,

Hussain³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

256

255

View full text Add to dashboard Cite

Proteolytic processing of the amyloid precursor protein (APP) by ␤-secretase, ␤-site APP cleaving enzyme (BACE1), is the initial step in the production of the amyloid ␤ (A␤) peptide, which is involved in the pathogenesis of Alzheimer's disease. The normal cellular function of the prion protein (PrP C ), the causative agent of the transmissible spongiform encephalopathies such as CreutzfeldtJakob disease in humans, remains enigmatic. Because both APP and PrP C are subject to proteolytic processing by the same zinc metalloproteases, we tested the involvement of PrP C in the proteolytic processing of APP. Cellular overexpression of PrP C inhibited the ␤-secretase cleavage of APP and reduced A␤ formation. Conversely, depletion of PrP C in mouse N2a cells by siRNA led to an increase in A␤ peptides secreted into the medium. In the brains of PrP knockout mice and in the brains from two strains of scrapieinfected mice, A␤ levels were significantly increased. Two mutants of PrP, PG14 and A116V, that are associated with familial human prion diseases failed to inhibit the ␤-secretase cleavage of APP. Using constructs of PrP, we show that this regulatory effect of PrP C on the ␤-secretase cleavage of APP required the localization of PrP C to cholesterol-rich lipid rafts and was mediated by the N-terminal polybasic region of PrP C via interaction with glycosaminoglycans. In conclusion, this is a mechanism by which the cellular production of the neurotoxic A␤ is regulated by PrP C and may have implications for both Alzheimer's and prion diseases.lipid raft ͉ proteolysis ͉ scrapie ͉ glycosaminoglycan A lzheimer's disease (AD) is characterized by the presence of extracellular senile plaques and intracellular neurofibrillary tangles within the afflicted brain. The major constituents of senile plaques are the amyloid ␤ (A␤) peptides, which are derived from the proteolytic processing of the amyloid precursor protein (APP) (1). In the amyloidogenic pathway, ␤-secretase cleavage of APP yields a soluble N-terminal fragment sAPP␤, along with a short membrane-bound C-terminal fragment that is subsequently cleaved by ␥-secretase to release the A␤ peptides. In the alternative, nonamyloidogenic pathway, ␣-secretase cleaves APP within the A␤ sequence, thus precluding the formation of A␤, and releases a soluble N-terminal fragment sAPP␣. The transmembrane aspartyl protease, ␤-site APP cleaving enzyme (BACE1), has been identified as ␤-secretase (2), members of the ADAM (a disintegrin and metalloprotease) family, particularly ADAM10 and ADAM17, are responsible for ␣-secretase cleavage (3), while a complex of at least four proteins, the presenilins, nicastrin, Aph-1, and Pen-2, constitutes the ␥-secretase (2).The prion protein (PrP) is the causative agent of the transmissible spongiform encephalopathies (TSEs) that include CreutzfeldtJakob disease (CJD), Gerstmann-Scheinker-Straussler (GSS) disease, kuru and fatal familial insomnia in humans, bovine spongiform encephalopathy in cattle, and scrapie in sheep (4). In these diseases, the normal ce...

show abstract

“…13 Nonetheless, recent studies providing evidence of 'asymptomatic infected carriers' in the UK population, as well as the fourth case of 'highly probable' transfusional cases already reported today are in favour of a possible 'underground propagation' of PrP sc within the human population. [14][15][16][17][18] Though its reality may be considered as evidenced, its extent and its evolution in the exposed populations, within such long delays of asymptomatic incubation and with possible lifelong asymptomatic carrier cases, are still very difficult to estimate. Therefore, diagnostic tests for the detection of PrP sc infection at onset are required for an efficient control of this disease.…”

mentioning

confidence: 99%

Rapid diagnosis of human prion disease using streptomycin with tonsil and brain tissues

Quadrio

Ugnon-Café

Dupin

et al. 2009

Laboratory Investigation

View full text Add to dashboard Cite

The use of streptomycin in the pathological prion protein (PrP sc ) detection procedures represents a new and attractive way for diagnostic purpose. With this agent, western blot readily detected PrP sc in 263K scrapie hamster and C57Bl/6 wild-type mice challenged with C506M3 scrapie strain. Our aim was to evaluate this new diagnosis procedure in the field of human transmissible spongiform encephalopathies (TSEs). First, we had confirmed the ability of streptomycin to precipitate PrP res from human brain of Creutzfeldt-Jakob disease (CJD) patient. Second, we compared the detection of PrP res with streptomycin against three other protocols using other precipitations. Then we assessed PrP res detection with streptomycin in 98 brain tissue samples from various aetiologies of human TSEs and 52 brain samples from other dementia. Finally, we applied this protocol for tonsils examination of five patients suspected of variant CJD (v-CJD). Sensitivity and specificity obtained with the streptomycin protocol were both 100% on brain tissue. For tonsil tissues, PrP res was clearly identified in the two post-mortem confirmed v-CJD cases, whereas no characteristic three-band pattern was seen in the three confirmed non-v-CJD samples. In this study, streptomycin demonstrated its efficiency to detect PrP res both in the central nervous system and in the lymphoid tissue without practical difficulty and with rapid preparation. Because of its ability to act as a good agent for PrP sc examination in different tissues, recovery of PrP sc in biological fluids using streptomycin should open further perspectives of applications in CJD diagnostics. Streptomycin effects in vivo might thus also be questioned.

show abstract

Predicting susceptibility and incubation time of human-to-human transmission of vCJD

Cited by 265 publications

References 30 publications

Characterization of Variant Creutzfeldt-Jakob Disease Prions in Prion Protein-humanized Mice Carrying Distinct Codon 129 Genotypes

Characterization of Variant Creutzfeldt-Jakob Disease Prions in Prion Protein-humanized Mice Carrying Distinct Codon 129 Genotypes

Cellular prion protein regulates β-secretase cleavage of the Alzheimer's amyloid precursor protein

Rapid diagnosis of human prion disease using streptomycin with tonsil and brain tissues

Contact Info

Product

Resources

About