PMCA generated prions from the olfactory mucosa of patients with Fatal Familial Insomnia cause prion disease in mice

Journal: 

Elife

Date: 

14 April, 2021

Authors: 

Edoardo Bistaffa, Alba Marín Moreno, Juan Carlos Espinosa, Chiara Maria Giulia De Luca, Federico Angelo Cazzaniga, Sara Maria Portaleone, Luigi Celauro, Giuseppe Legname, Giorgio Giaccone, Juan Maria Torres, Fabio Moda

Abstract

Background: Fatal Familial Insomnia (FFI) is a genetic prion disease caused by the D178N mutation in the prion protein gene (PRNP) in coupling phase with methionine at PRNP 129. In 2017, we have shown that the olfactory mucosa (OM) collected from FFI patients contained traces of PrPScdetectable by Protein Misfolding Cyclic Amplification (PMCA).

Methods In this work, we have challenged PMCA generated products obtained from OM and brain homogenate of FFI patients in BvPrP-Tg407 transgenic mice expressing the bank vole prion protein to test their ability to induce prion pathology.

Results: All inoculated mice developed mild spongiform changes, astroglial activation and PrPScdeposition mainly affecting the thalamus. However, their neuropathological alterations were different from those found in the brain of BvPrP-Tg407 mice injected with raw FFI brain homogenate.

Conclusions: Although with some experimental constraints, we show that PrPSc present in OM of FFI patients is potentially infectious.