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 PrP(Sc) in the brain. Here, for the first time, we demonstrate that the olfactory mucosa (OM) of patients with FFI contains trace amount of PrP(Sc) detectable by PMCA and RT-QuIC. Quantitative PMCA analysis estimated a PrP(Sc) concentration of about 1 × 10(-14) g/ml. In contrast, PrP(Sc) 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 PrP(Sc) oligomer/molecule with a specificity of 100%.

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

ZANUSSO, Gianluigi;SACCHETTO, Luca;
2017

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 PrP(Sc) in the brain. Here, for the first time, we demonstrate that the olfactory mucosa (OM) of patients with FFI contains trace amount of PrP(Sc) detectable by PMCA and RT-QuIC. Quantitative PMCA analysis estimated a PrP(Sc) concentration of about 1 × 10(-14) g/ml. In contrast, PrP(Sc) 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 PrP(Sc) oligomer/molecule with a specificity of 100%.
Fatal Familial Insomnia; olfactory mucosa; PrPSc; detection; specificity
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/960151
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