This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kulkarni, R. V. Articles by Pázmándi, F. Search for Related Content PubMed PubMed Citation Articles by Kulkarni, R. V. Articles by Pázmándi, F.

Theoretical Modeling of Prion Disease Incubation

R. V. Kulkarni ^*, A. Slepoy , R. R. P. Singh ^*, D. L. Cox ^* and F. Pázmándi ^*

^* Department of Physics, University of California, Davis, California; and Sandia National Laboratories, Albuquerque, New Mexico

Correspondence: Address reprint requests to R. V. Kulkarni, Tel.: 609-951-2888; Fax: 609-951-2496; E-mail: kulkarni{at}physics.ucdavis.edu.

We apply a theoretical aggregation model to laboratory and epidemiological prion disease incubation time data. In our model, slow growth of misfolded protein aggregates from small initial seeds controls the latent or lag phase; aggregate fissioning and subsequent spreading leads to an exponential growth phase. Our model accounts for the striking reproducibility of incubation times for high dose inoculation of lab animals. In particular, low dose yields broad incubation time distributions, and increasing dose narrows distributions and yields sharply defined onset times. We also explore how incubation time statistics depend upon aggregate morphology. We apply our model to fit the experimental dose-incubation curves for distinct strains of scrapie, and explain logarithmic variation at high dose and deviations from logarithmic behavior at low dose. We use this to make testable predictions for infectivity time-course experiments.

This article has been cited by other articles:

				D.-M. Ou, C.-C. Chen, and C.-M. Chen Contact-Induced Structure Transformation in Transmembrane Prion Propagation Biophys. J., April 15, 2007; 92(8): 2704 - 2710. [Abstract] [Full Text] [PDF]

				D. L. Cox, R. R. P. Sing, and S. Yang Prion Disease: Exponential Growth Requires Membrane Binding Biophys. J., June 1, 2006; 90(11): L77 - L79. [Abstract] [Full Text] [PDF]

				D. L. Mobley, D. L. Cox, R. R. P. Singh, R. V. Kulkarni, and A. Slepoy Simulations of Oligomeric Intermediates in Prion Diseases Biophys. J., October 1, 2003; 85(4): 2213 - 2223. [Abstract] [Full Text] [PDF]