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Background: Human prion diseases, known collectively as Creutzfeldt-Jakob disease (CJD), are fatal, infectious neurodegenerative disorders that occur in all human populations.Objective: To summarize national surveillance data for CJD in Canada between January 1, 1998, and December 31, 2013.Methods: Detailed investigations were conducted of individual suspected CJD cases, with collaboration between Canadian health professionals and investigators affiliated with a central CJD surveillance registry operated by the Public Health Agency of Canada. Data were collected on the clinical profile, family history, and results of paraclinical and laboratory investigations, including post-mortem neuropathological examination.Results: A total of 662 deaths from definite and probable CJD were identified in Canadian residents during the study period, comprising 613 cases of sporadic CJD (92.6%), 43 cases of genetic prion disease (6.5%), 4 cases of iatrogenic CJD (0.6%), and 2 cases of variant CJD disease (0.3%). The overall crude mortality rate for sporadic CJD was 1.18 per million per year [95% confidence interval (CI): 1.08,1.27]. Age-specific rates ranged from 0.05 [95% CI: 0.03,0.08] in persons under 50 years of age to 7.11 [95% CI: 6.20,8.11] in those aged 70 to 79. A significant net upward trend in age-adjusted rates was observed over the study period. Standardized mortality ratios, calculated for 10 individual Canadian provinces with reference to national average mortality rates, did not differ significantly from 1.0.Conclusion: Creutzfeldt-Jakob disease remains rare in Canada, although mortality rates vary by two orders of magnitude between older and younger age groups. The upward trend in age-standardized sporadic CJD mortality rate over the study period can be better accounted for by gradually improving case ascertainment than by a real increase in incidence. [ABSTRACT FROM AUTHOR]

Human prion diseases are characterized by the accumulation in the brain of proteinase K (PK)-resistant prion protein designated PrP27 – 30 detectable by the 3F4 antibody against human PrP109 – 112. We recently identified a new PK-resistant PrP species, designated PrP*20, in uninfected human and animal brains. It was preferentially detected with the 1E4 antibody against human PrP 97 – 108 but not with the anti-PrP 3F4 antibody, although the 3F4 epitope is adjacent to the 1E4 epitope in the PrP*20 molecule. The present study reveals that removal of the N-terminal amino acids up to residue 91 significantly increases accessibility of the 1E4 antibody to PrP of brains and cultured cells. In contrast to cells expressing wild-type PrP, cells expressing pathogenic mutant PrP accumulate not only PrP*20 but also a small amount of 3F4-detected PK-resistant PrP27 – 30. Remarkably, during the course of human prion disease, a transition from an increase in 1E4-detected PrP*20 to the occurrence of the 3F4-detected PrP27 – 30 was observed. Our study suggests that an increase in the level of PrP*20 characterizes the early stages of prion diseases. [ABSTRACT FROM AUTHOR]