Unhampered prion neuroinvasion despite impaired fast axonal transport in transgenic mice overexpressing four-repeat tau.
Transmissible spongiform encephalopathies often are caused by peripheral uptake of infectious prions, and the peripheral nervous system is involved in prion spread to the brain. Although the cellular prion protein is subjected to fast axonal transport, the mechanism of intranerval transport of infectious prions is unclear. Here we administered prions intranervally to transgenic mice overexpressing the four-repeat human tau protein, which exhibit defective fast axonal transport. These mice showed unaltered neuroinvasion, suggesting that transport mechanisms distinct from fast axonal transport effect prion neuroinvasion along peripheral nerves. Surprisingly, scrapie-sick tau transgenic mice accumulated intraneuronal deposits of hyperphosphorylated tau protein. The coincidence of tau and prion pathology resembled Gerstmann-Sträussler-Scheinker syndrome. These findings identify tau pathology as a possible end stretch of prion-induced neurodegeneration.
Institute of Neuropathology, University Hospital Zürich, CH-8091 Zürich, Switzerland.
Valerie
V
Künzi
Markus
M
Glatzel
Michel Y
MY
Nakano
Urs F
UF
Greber
Fred
F
Van Leuven
Adriano
A
Aguzzi
D000818:Animals; D001370:Axonal Transport; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D018450:Disease Progression; D005727:Ganglia, Spinal / Q000737:chemistry; D016098:Gerstmann-Straussler-Scheinker Disease / Q000473:pathology / Q000503:physiopathology / Q000635:transmission; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010525:Peripheral Nerves / Q000503:physiopathology; D010766:Phosphorylation; D018620:PrPSc Proteins / Q000472:pathogenicity; D017096:Prion Diseases / Q000473:pathology / Q000503:physiopathology* / Q000635:transmission; D011328:Prions / Q000032:analysis / Q000472:pathogenicity / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D013154:Spleen / Q000737:chemistry / Q000473:pathology; D015996:Survival Rate; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
D018620:PrPSc Proteins; D011328:Prions; D020033:Protein Isoforms; D016875:tau Proteins