Theoretical modeling of prion disease incubation

Abstract

We present a theory for the laboratory and epidemiological data for incubation times in infectious prion diseases. The central feature of our model is that slow growth of misfolded protein-aggregates from small initial seeds controls the `latent' or `lag' phase, whereas aggregate-fissioning and subsequent spreading leads to an exponential growth or doubling phase. Such a general framework can account for many features of prion diseases including the striking reproducibility of incubation times when high doses are inoculated into lab animals. Broad incubation time distributions arise for low infectious dose, while our calculated distributions narrow to sharply defined onset times with increased dose. We apply our distributions to epidemiological vCJD data and extract estimates of incubation times.