Ubiquitin C-hydrolase L1 as a cerebrospinal fluid and blood biomarker for prion diseases.

Digital enzyme-linked immunosorbent assays are based on single-molecule array technology. In this study, ubiquitin C-terminal hydrolase L1 (UCH-L1) levels were measured in cerebrospinal fluid (CSF) and blood samples (serum or plasma) obtained from patients with sporadic Creutzfeldt-Jakob disease and fatal familial insomnia using a commercially available UCH-L1 assay. We determined the inter- and intra-assay variability as well as the stability of UCH-L1 detection to ensure a reliable assay performance. Cut-off values were calculated to differentiate prion disease patients from neurodegenerative and non-neurodegenerative control groups. Patients with Creutzfeldt-Jakob disease exhibited significantly higher levels of UCH-L1 in both CSF and serum than controls. Receiver operating characteristic (ROC) analysis yielded area under the curve (AUC) values ranging from 0.91 to 0.97 for CSF and from 0.58 to 0.86 for serum. These values allow an excellent discrimination between Creutzfeldt-Jakob disease patients and controls. Similar findings were observed in the fatal familial insomnia cohort. Here, ROC analysis indicated AUC values between 0.79 and 0.91 for CSF and up to 0.95 for plasma when distinguishing fatal familial insomnia patients from neurodegenerative, non-neurodegenerative and healthy controls. Altogether, our study suggests that detection of UCH-L1 levels in CSF and blood is suitable for the diagnosis of prion diseases.