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.
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 PrP in the brain. Here, for the first time, we demonstrate that the olfactory mucosa (OM) of patients with FFI contains trace amount of PrP detectable by PMCA and RT-QuIC. Quantitative PMCA analysis estimated a PrP concentration of about 1 × 10 g/ml. In contrast, PrP 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 oligomer/molecule with a specificity of 100%.
致命家族性失眠症（FFI）是一种由朊病毒蛋白基因（PRNP）中的点突变引起的遗传性朊病毒病，其特征为明显的丘脑萎缩、弥漫性星形胶质增生和脑内 PrP 的适度沉积。在这里，我们首次证明 FFI 患者的嗅黏膜（OM）中含有可通过 PMCA 和 RT-QuIC 检测到的痕量 PrP。定量 PMCA 分析估计 PrP 浓度约为 1×10-9g/ml。相比之下，OM 样本中未检测到来自健康对照者和其他神经退行性疾病（包括阿尔茨海默病、帕金森病和额颞叶痴呆）患者的 PrP。这些结果表明，这些检测方法的检测限为单个 PrP 低聚物/分子的数量级，特异性为 100%。
