In contrast with other
neurodegenerative disorders associated to
protein misfolding, human
prion diseases include infectious forms (also called transmitted forms) such as
kuru, iatrogenic
Creutzfeldt-Jakob disease and
variant Creutzfeldt-Jakob disease. The transmissible agent is thought to be solely composed of the abnormal
isoform (PrP(Sc)) of the host-encoded
prion protein that accumulated in the central nervous system of affected individuals. Compared to its normal counterpart, PrP(Sc) is β-sheet enriched and aggregated and its propagation is based on an autocatalytic conversion process. Increasing evidence supports the view that conformational variations of PrP(Sc) encoded the
biological properties of the various
prion strains that have been isolated by transmission studies in experimental models. Infectious forms of human
prion diseases played a pivotal role in the emergence of the
prion concept and in the characterization of the very unconventional properties of
prions. They provide a unique model to understand how
prion strains are selected and propagate in humans. Here, we review and discuss how genetic factors interplay with strain properties and route of transmission to influence
disease susceptibility, incubation period and phenotypic expression in the light of the
kuru epidemics due to ritual endocannibalism, the various series
iatrogenic diseases secondary to extractive
growth hormone treatment or dura mater graft and the epidemics of
variant Creutzfeldt-Jakob disease linked to dietary exposure to the agent of
bovine spongiform encephalopathy.