We have developed a novel real‐time quaking‐induced conversion RT‐QuIC‐based assay to detect alpha‐synuclein aggregation in brain and cerebrospinal fluid from dementia with Lewy bodies and Parkinson's disease patients. This assay can detect alpha‐synuclein aggregation in Dementia with Lewy bodies and Parkinson's disease cerebrospinal fluid with sensitivities of 92% and 95%, respectively, and with an overall specificity of 100% when compared to Alzheimer and control cerebrospinal fluid. Patients with neuropathologically confirmed tauopathies (progressive supranuclear palsy; corticobasal degeneration) gave negative results. These results suggest that RT‐QuiC analysis of cerebrospinal fluid is potentially useful for the early clinical assessment of patients with alpha‐synucleinopathies.

Objective: Current cerebrospinal fluid (CSF) tests for sporadic Creutzfeldt–Jakob disease (sCJD) are based on the detection of surrogate markers of neuronal damage such as CSF 14‐3‐3, which are not specific for sCJD. A number of prion protein conversion assays have been developed, including real time quaking‐induced conversion (RT‐QuIC). The objective of this study is to investigate whether CSF RT‐QuIC analysis could be used as a diagnostic test in sCJD. Methods: An exploratory study was undertaken that analyzed 108 CSF samples from patients with neuropathologically confirmed sCJD or from control patients. Of the 108 CSF samples, 56 were from sCJD patients (30 female, 26 male; aged 31–84 years; mean age, 62.3 ± 13.5 years), and 52 were from control patients (26 female, 26 male; aged 43–84 years; mean age, 67.8 ± 10.4 years). A confirmatory group of 118 patients was subsequently examined that consisted of 67 cases of neuropathologically confirmed sCJD (33 female, 34 male; aged 39–82 years; mean age, 67.5 ± 9.0 years) and 51 control cases (26 female, 25 male; aged 36–87 years; mean age, 63.5 ± 11.6 years). Results: The exploratory study showed that RT‐QuIC analysis had a sensitivity of 91% and a specificity of 98% for the diagnosis of sCJD. These results were confirmed in the confirmatory study, which showed that CSF RT‐QuIC analysis had a sensitivity and specificity of 87% and 100%, respectively. Interpretation: This study shows that CSF RT‐QuIC analysis has the potential to be a more specific diagnostic test for sCJD than current CSF tests. ANN NEUROL 2012;72:278–285.

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