TY - JOUR TI - PMCA-generated prions from the olfactory mucosa of patients with Fatal Familial Insomnia cause prion disease in mice AU - Bistaffa, Edoardo AU - Marín-Moreno, Alba AU - Espinosa, Juan Carlos AU - De Luca, Chiara Maria Giulia AU - Cazzaniga, Federico Angelo AU - Portaleone, Sara Maria AU - Celauro, Luigi AU - Legname, Giuseppe AU - Giaccone, Giorgio AU - Torres, Juan Maria AU - Moda, Fabio A2 - Taylor, J Paul A2 - Zaidi, Mone A2 - Chen, Shu VL - 10 PY - 2021 DA - 2021/04/14 SP - e65311 C1 - eLife 2021;10:e65311 DO - 10.7554/eLife.65311 UR - https://doi.org/10.7554/eLife.65311 AB - 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 PrPSc detectable 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 PrPSc deposition 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. Funding:. This work was supported in part by the Italian Ministry of Health (GR-2013-02355724 and Ricerca Corrente), MJFF, ALZ, Alzheimer’s Research UK and the Weston Brain Institute (BAND2015), and Euronanomed III (SPEEDY) to FM; by the Spanish Ministerio de Economía y Competitividad (grant AGL2016-78054-R [AEI/FEDER, UE]) to JMT and JCE; AM-M was supported by a fellowship from the INIA (FPI-SGIT-2015-02). KW - fatal familial insomnia KW - olfactory mucosa KW - protein misfolding cyclic amplification KW - transmission studies KW - neurodegeneration KW - prion JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -