title: Detection of prion seeding activity in the olfactory mucosa of patients with Fatal Familial Insomnia.
abstract: 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 PrPScin the brain. Here, for the first time, we demonstrate that the olfactory mucosa (OM) of patients with FFI contains trace amount of PrPScdetectable by PMCA and RT-QuIC. Quantitative PMCA analysis estimated a PrPScconcentration of about 1 × 10-14g/ml. In contrast, PrPScwas 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 PrPScoligomer/molecule with a specificity of 100%.
authors.affiliation: IRCCS Foundation Carlo Besta Neurological Institute, Department of Neurology 5 and Neuropathology, Milan, Italy.
authors.forename: Veronica
authors.initials: V
authors.lastname: Redaelli
authors.affiliation: IRCCS Foundation Carlo Besta Neurological Institute, Department of Neurology 5 and Neuropathology, Milan, Italy.|Scuola Internazionale Superiore di Studi Avanzati (SISSA), Department of Neuroscience, Trieste, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Bistaffa
authors.affiliation: University of Verona, Department of Neurosciences, Biomedicine and Movement Sciences, Verona, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Zanusso
authors.affiliation: Scuola Internazionale Superiore di Studi Avanzati (SISSA), Department of Neuroscience, Trieste, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Salzano
authors.affiliation: University of Verona, Otolaryngology department, Verona, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Sacchetto
authors.affiliation: IRCCS Foundation Carlo Besta Neurological Institute, Department of Neurology 5 and Neuropathology, Milan, Italy.|Scuola Internazionale Superiore di Studi Avanzati (SISSA), Department of Neuroscience, Trieste, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Rossi
authors.affiliation: IRCCS Foundation Carlo Besta Neurological Institute, Department of Neurology 5 and Neuropathology, Milan, Italy.
authors.forename: Chiara Maria Giulia
authors.initials: CM
authors.lastname: De Luca
authors.affiliation: Istituto Superiore di Sanità, Department of Veterinary Public Health and Food Safety, Rome, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Di Bari
authors.affiliation: Otolaryngology Unit, San Paolo Hospital, Department of Health Sciences, University of Milan, Milan, Italy.
authors.forename: Sara Maria
authors.initials: SM
authors.lastname: Portaleone
authors.affiliation: Istituto Superiore di Sanità, Department of Veterinary Public Health and Food Safety, Rome, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Agrimi
authors.affiliation: Scuola Internazionale Superiore di Studi Avanzati (SISSA), Department of Neuroscience, Trieste, Italy.|ELETTRA Laboratory, Sincrotrone Trieste S.C.p.A., Trieste, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Legname
authors.affiliation: ASL9 Ca'Foncello, Treviso, Italy.
authors.forename: Ignazio
authors.initials: I
authors.lastname: Roiter
authors.affiliation: IRCCS Foundation Istituto di Ricerche Farmacologiche Mario Negri, Department of Neuroscience, Milan, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
authors.affiliation: IRCCS Foundation Carlo Besta Neurological Institute, Department of Neurology 5 and Neuropathology, Milan, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tagliavini
authors.affiliation: IRCCS Foundation Carlo Besta Neurological Institute, Department of Neurology 5 and Neuropathology, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Moda
mesh_terms: D016022:Case-Control Studies; D006801:Humans; D034062:Insomnia, Fatal Familial / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D009831:Olfactory Mucosa / Q000378:metabolism*; D018620:PrPSc Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D018620:PrPSc Proteins