Silent prions lying in wait: a two-hit model of prion/amyloid formation and infection.
Diseases such as type 2 diabetes, Alzheimer's and Parkinson's are associated with the formation of amyloid. The transmissible spongiform encephalopathies, such as variant Creutzfeldt-Jakob disease, are believed to result from infectious forms of amyloid proteins termed prions. The ability of amyloid to initiate spontaneously and in the case of prions, to transfer successfully from one host to another, has been hard to fully rationalize. In this paper we use a mathematical model to explore the idea that it might be a combination of the presence of the prion/amyloid form and a change in the state of the host that allows the amyloid/prion to successfully initiate and propagate itself. We raise the intriguing possibility that potentially infectious amyloid may lie dormant in an apparently healthy individual awaiting a change in the state of the host or transmittal to a new more susceptible host. On this basis we make an analogy between prion/amyloid disease development and the two-hit model of cancer progression. We additionally raise the possibility that infectious amyloid strains may be characterized by a size distribution of length or radius.
Hall
Damien
D
Laboratory of Biochemistry and Genetics, National Institute of Diabetes Digestive and Kidney Diseases, National Institutes of Health Bethesda, MD 20892-0830, USA. drh32@cam.ac.uk
Edskes
Herman
H
D000682:Amyloid / Q000378:metabolism*; D017772:Amyloid Neuropathies / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D018562:Disease Transmission, Infectious; D006801:Humans; D008962:Models, Theoretical; D017096:Prion Diseases / Q000378:metabolism*; D011328:Prions / Q000378:metabolism*; D012756:Sheep
D000682:Amyloid; D011328:Prions