Title | Greater specificity for cerebrospinal fluid P-tau231 over P-tau181 in the differentiation of healthy controls from Alzheimer's disease. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Spiegel, J, Pirraglia, E, Osorio, RS, Glodzik, L, Li, Y, Tsui, W, Louis, LASaint, Randall, C, Butler, T, Xu, J, Zinkowski, RP, Zetterberg, H, Fortea, J, Fossati, S, Wisniewski, T, Davies, P, Blennow, K, de Leon, MJ |
Journal | J Alzheimers Dis |
Volume | 49 |
Issue | 1 |
Pagination | 93-100 |
Date Published | 2016 |
ISSN | 1875-8908 |
Keywords | Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Biomarkers, Case-Control Studies, Cross-Sectional Studies, Female, Humans, Logistic Models, Male, Middle Aged, Phosphorylation, ROC Curve, Sensitivity and Specificity, tau Proteins |
Abstract | Cerebrospinal fluid (CSF) measures of phosphorylated-tau (P-tau) 231 and P-tau181 are two biomarkers for the identification of tau pathology as related to Alzheimer's disease (AD). While both are pathologically validated, their relative diagnostic performances are not well known. This cross-sectional diagnostic study of 87 normal (NL) subjects and 28 AD subjects compared CSF P-tau231 with CSF P-tau181. Logistic regression modeling demonstrated that the P-tau231 was superior to the P-tau181 in the diagnostic classifications. At a fixed 85% sensitivity cutoff, the ROC analysis shows that P-tau231 has greater overall specificity than P-tau181. While both P-tau analytes demonstrated equivalent negative predictive accuracies, P-tau231 yielded significantly fewer false positives. Moreover, P-tau231, but not P-tau181, demonstrated sensitivity to the E4 genotype. A postmortem validation with 9 AD subjects confirmed the superiority of the CSF P-tau231 specificity. This study suggests that P-tau231 has the potential to improve the CSF tau biomarker diagnosis of AD. |
DOI | 10.3233/JAD-150167 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 26444757 |
PubMed Central ID | PMC4694576 |
Grant List | R01 AG022374 / AG / NIA NIH HHS / United States R01 HL111724 / HL / NHLBI NIH HHS / United States R01 AG035137 / AG / NIA NIH HHS / United States HL111724 / HL / NHLBI NIH HHS / United States AG035137 / AG / NIA NIH HHS / United States R21 AG032554 / AG / NIA NIH HHS / United States R01 AG013616 / AG / NIA NIH HHS / United States P30 AG008051 / AG / NIA NIH HHS / United States R01 AG012101 / AG / NIA NIH HHS / United States AG022374 / AG / NIA NIH HHS / United States AG032554 / AG / NIA NIH HHS / United States AG13616 / AG / NIA NIH HHS / United States AG08051 / AG / NIA NIH HHS / United States AG12101 / AG / NIA NIH HHS / United States |