Detection of prion seeding activity in the olfactory mucosa of patients with Fatal Familial Insomnia


Scientific Reports


7 April, 2017


Veronica Redaelli, Edoardo Bistaffa, Gianluigi Zanusso, Giulia Salzano, Luca Sacchetto, Martina Rossi, Chiara Maria Giulia De Luca, Michele Di Bari, Sara Maria Portaleone, Umberto Agrimi, Giuseppe Legname, Ignazio Roiter, Gianluigi Forloni, Fabrizio Tagliavini & Fabio Moda

Sci Rep. 2017 Apr 7;7:46269. doi: 10.1038/srep46269


Fatal Familial Insomnia (FFI) is a genetic prion disease caused by a point mutation in the prion protein gene (PRNP) characterized by prominent thalamic atrophy, diffuse astrogliosis and moderate deposition of PrPSc in the brain. Here, for the first time, we demonstrate that the olfactory mucosa (OM) of patients with FFI contains trace amount of PrPSc detectable by PMCA and RT-QuIC. Quantitative PMCA analysis estimated a PrPSc concentration of about 1 × 10−14 g/ml. In contrast, PrPSc was not detected in OM samples from healthy controls and patients affected by other neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease and frontotemporal dementia. These results indicate that the detection limit of these assays is in the order of a single PrPSc oligomer/molecule with a specificity of 100%.