decreased csf transferrin in scjd a potential pre-mortem diagnostic test for prion disorders减少脑脊液转铁蛋白在scjd潜在pre-mortem朊病毒疾病的诊断测试.pdfVIP

Decreased CSF Transferrin in sCJD: A Potential Pre-Mortem Diagnostic Test for Prion Disorders 1. 2. 1 Ajay Singh , 9Alim J. Beveridge , Neena Singh * 1 Department of Pathology, Case Western Reserve University, Cleveland, Ohio, United States of America, 2 Department of Organizational Behavior, Case Western Reserve University, Cleveland, Ohio, United States of America Abstract Sporadic Creutzfeldt-Jakob-disease (sCJD) is a fatal neurodegenerative condition that escapes detection until autopsy. Recently, brain iron dyshomeostasis accompanied by increased transferrin (Tf) was reported in sCJD cases. The consequence of this abnormality on cerebrospinal-fluid (CSF) levels of Tf is uncertain. We evaluated the accuracy of CSF Tf, a ‘new’ biomarker, as a pre-mortem diagnostic test for sCJD when used alone or in combination with the ‘current’ biomarker total- tau (T-tau). Levels of total-Tf (T-Tf), isoforms of Tf (Tf-1 and Tf-b2), and iron saturation of Tf were quantified in CSF collected 0.3–36 months before death (duration) from 99 autopsy confirmed sCJD (CJD+) and 75 confirmed cases of dementia of non- CJD origin (CJD-). Diagnostic accuracy was estimated by non-parametric tests, logistic regression, and receiver operating characteristic (ROC) analysis. Area under the ROC curve (AUC), sensitivity, specificity, positive and negative predictive values (PV), and likelihood ratios (LR) of each biomarker and biomarker combination were calculated. We report that relative to CJD-, CJD+ cases had lower median CSF T-Tf (125,7093 vs. 217,7893) and higher T-tau (11530 vs. 1266) values. AUC was 0.90 (95% confidence interval (CI), 0.85–0.94) for T-Tf, and 0.93 (95% CI, 0.89–0.97) for T-Tf combined with T-tau. With cut-offs defined to achieve a sensitivity of ,85%, T-Tf identifie