Greater specificity for cerebrospinal fluid P-tau231 over P-tau181 in the differentiation of healthy controls from Alzheimer's disease.

Publication Type Academic Article
Authors Spiegel J, Pirraglia E, Osorio R, Glodzik L, Li Y, Tsui W, Saint Louis L, Randall C, Butler T, Xu J, Zinkowski R, Zetterberg H, Fortea J, Fossati S, Wisniewski T, Davies P, Blennow K, de Leon M
Journal J Alzheimers Dis
Volume 49
Issue 1
Pagination 93-100
Date Published 01/01/2016
ISSN 1875-8908
Keywords Alzheimer Disease, Amyloid beta-Peptides, 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
PubMed ID 26444757
PubMed Central ID PMC4694576
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