TY - JOUR
T1 - Decreased csf transferrin in scjd
T2 - A potential pre-mortem diagnostic test for prion disorders
AU - Singh, Ajay
AU - Beveridge, Alim J.
AU - Singh, Neena
PY - 2011
Y1 - 2011
N2 - 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-β2), 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 identified CJD+ cases with a specificity of 71.6% (95% CI, 59.1-81.7), positive LR of 3.0 (95% CI, 2.1-4.5), negative LR of 0.2 (95% CI, 0.1-0.3), and accuracy of 80.1%. The effect of patient age and duration was insignificant. T-Tf combined with T-tau identified CJD+ with improved specificity of 87.5% (95%CI, 76.3-94.1), positive LR of 6.8 (95% CI, 3.5-13.1), negative LR of 0.2 (95% CI, 0.1-0.3), positive-PV of 91.0%, negative-PV of 80.0%, and accuracy of 86.2%. Thus, CSF T-Tf, a new biomarker, when combined with the current biomarker T-tau, is a reliable pre-mortem diagnostic test for sCJD.
AB - 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-β2), 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 identified CJD+ cases with a specificity of 71.6% (95% CI, 59.1-81.7), positive LR of 3.0 (95% CI, 2.1-4.5), negative LR of 0.2 (95% CI, 0.1-0.3), and accuracy of 80.1%. The effect of patient age and duration was insignificant. T-Tf combined with T-tau identified CJD+ with improved specificity of 87.5% (95%CI, 76.3-94.1), positive LR of 6.8 (95% CI, 3.5-13.1), negative LR of 0.2 (95% CI, 0.1-0.3), positive-PV of 91.0%, negative-PV of 80.0%, and accuracy of 86.2%. Thus, CSF T-Tf, a new biomarker, when combined with the current biomarker T-tau, is a reliable pre-mortem diagnostic test for sCJD.
UR - http://www.scopus.com/inward/record.url?scp=79952400329&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0016804
DO - 10.1371/journal.pone.0016804
M3 - Article
C2 - 21408069
AN - SCOPUS:79952400329
SN - 1932-6203
VL - 6
JO - PLoS ONE
JF - PLoS ONE
IS - 3
M1 - e16804
ER -
