Prion pathogenesis is unaltered in a mouse strain with a permeable blood-brain barrier

Annika Keller, Mario Nuvolone, Irina Abakumova, Andra Chincisan, Regina Reimann, Merve Avar, Daniel Heinzer, Simone Hornemann, Josephin Wagner, Daniel Kirschenbaum, Fabian F. Voigt, Caihong Zhu, Luca Regli, Fritjof Helmchen, Adriano Aguzzi

Research output: Contribution to journalArticlepeer-review


Transmissible spongiform encephalopathies (TSEs) are caused by the prion, which consists essentially of PrPSc, an aggregated, conformationally modified form of the cellular prion protein (PrPC). Although TSEs can be experimentally transmitted by intracerebral inoculation, most instances of infection in the field occur through extracerebral routes. The epidemics of kuru and variant Creutzfeldt-Jakob disease were caused by dietary exposure to prions, and parenteral administration of prion-contaminated hormones has caused hundreds of iatrogenic TSEs. In all these instances, the development of postexposure prophylaxis relies on understanding of how prions propagate from the site of entry to the brain. While much evidence points to lymphoreticular invasion followed by retrograde transfer through peripheral nerves, prions are present in the blood and may conceivably cross the blood-brain barrier directly. Here we have addressed the role of the blood-brain barrier (BBB) in prion disease propagation using Pdgfbret/ret mice which possess a highly permeable BBB. We found that Pdgfbret/ret mice have a similar prion disease incubation time as their littermate controls regardless of the route of prion transmission. These surprising results indicate that BBB permeability is irrelevant to the initiation of prion disease, even when prions are administered parenterally.

Original languageEnglish
Pages (from-to)e1007424
JournalPLoS Pathogens
Issue number11
Publication statusPublished - Nov 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology


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