Orrú CD, Bongianni M, Tonoli G, Ferrari S, Hughson AG, Groveman BR, Fiorini M, Pocchiari M, Monaco S, Caughey B, and Zanusso G
Background: Definite diagnosis of sporadic Creutzfeldt-Jakob disease in living patients remains a challenge. A test that detects the specific marker for Creutzfeldt-Jakob disease, the prion protein (PrP(CJD)), by means of real-time quaking-induced conversion (RT-QuIC) testing of cerebrospinal fluid has a sensitivity of 80 to 90% for the diagnosis of sporadic Creutzfeldt-Jakob disease. We have assessed the accuracy of RT-QuIC analysis of nasal brushings from olfactory epithelium in diagnosing sporadic Creutzfeldt-Jakob disease in living patients., Methods: We collected olfactory epithelium brushings and cerebrospinal fluid samples from patients with and patients without sporadic Creutzfeldt-Jakob disease and tested them using RT-QuIC, an ultrasensitive, multiwell plate-based fluorescence assay involving PrP(CJD)-seeded polymerization of recombinant PrP into amyloid fibrils., Results: The RT-QuIC assays seeded with nasal brushings were positive in 30 of 31 patients with Creutzfeldt-Jakob disease (15 of 15 with definite sporadic Creutzfeldt-Jakob disease, 13 of 14 with probable sporadic Creutzfeldt-Jakob disease, and 2 of 2 with inherited Creutzfeldt-Jakob disease) but were negative in 43 of 43 patients without Creutzfeldt-Jakob disease, indicating a sensitivity of 97% (95% confidence interval [CI], 82 to 100) and specificity of 100% (95% CI, 90 to 100) for the detection of Creutzfeldt-Jakob disease. By comparison, testing of cerebrospinal fluid samples from the same group of patients had a sensitivity of 77% (95% CI, 57 to 89) and a specificity of 100% (95% CI, 90 to 100). Nasal brushings elicited stronger and faster RT-QuIC responses than cerebrospinal fluid (P<0.001 for the between-group comparison of strength of response). Individual brushings contained approximately 10(5) to 10(7) prion seeds, at concentrations several logs10 greater than in cerebrospinal fluid., Conclusions: In this preliminary study, RT-QuIC testing of olfactory epithelium samples obtained from nasal brushings was accurate in diagnosing Creutzfeldt-Jakob disease and indicated substantial prion seeding activity lining the nasal vault. (Funded by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases and others.).