Prion diseases are a group of inevitably fatal
neurodegenerative disorders affecting numerous mammalian species, including humans. The existence of heritable phenotypes of disease in the natural host suggested that
prions exist as distinct strains. Transmission of sheep
scrapie to rodent models accelerated
prion research, resulting in the isolation and characterization of numerous strains with distinct characteristics. These strains are grouped into categories based on the incubation period of disease in different strains of mice and also by how stable the strain properties were upon serial passage. These classical studies defined the host and agent parameters that affected strain properties, and, prior to the advent of the
prion hypothesis, strain properties were hypothesized to be the result of mutations in a
nucleic acid genome of a conventional pathogen. The development of the
prion hypothesis challenged the paradigm of infectious agents, and, initially, the existence of strains was difficult to reconcile with a
protein-only agent. In the decades since, much evidence has revealed how a
protein-only infectious agent can perform complex
biological functions. The prevailing hypothesis is that strain-specific conformations of PrPSc encode
prion strain diversity. This hypothesis can provide a mechanism to explain the observed strain-specific differences in incubation period of disease, biochemical properties of PrPSc, tissue tropism, and subcellular patterns of pathology. This hypothesis also explains how
prion strains mutate, evolve, and adapt to new species. These concepts are applicable to
prion-like diseases such as Parkinson's and
Alzheimer's disease, where evidence of strain diversity is beginning to emerge.