Here it is shown that during the silent phase of prion infection, prions first exponentially propagate until a defined limit is reached. Then a plateau phase follows. Prion propagation is independent of prion concentration, whereas in the plateau phase the time to clinical onset is inversely correlated to prion concentration. The similar levels of infectivity at the end of the first and second phase suggests that there is a separation between prion infectivity and toxicity. Moreover, something seems to limit prion production. It is suggested that the prions are not neurotoxic themselves but catalyse the formation of such species from PrPC. Production of neurotoxic species is triggered when prion propagation saturates, leading to a switch from autocatalytic production of infectivity to a toxic pathway.
- Malin K. Sandberg
- Huda Al-Doujaily
- John Collinge
