title: Greater specificity for cerebrospinal fluid P-tau231 over P-tau181 in the differentiation of healthy controls from Alzheimer's disease.
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.
authors.affiliation: New York University, School of Medicine, Center for Brain Health, New York, NY, USA.|Wellington C. Mepham High School, Bellmore, NY, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Spiegel
authors.affiliation: New York University, School of Medicine, Center for Brain Health, New York, NY, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pirraglia
authors.affiliation: New York University, School of Medicine, Center for Brain Health, New York, NY, USA.
authors.forename: Ricardo S
authors.initials: RS
authors.lastname: Osorio
authors.affiliation: New York University, School of Medicine, Center for Brain Health, New York, NY, USA.
authors.forename: Lidia
authors.initials: L
authors.lastname: Glodzik
authors.affiliation: New York University, School of Medicine, Center for Brain Health, New York, NY, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: New York University, School of Medicine, Center for Brain Health, New York, NY, USA.
authors.forename: Wai
authors.initials: W
authors.lastname: Tsui
authors.affiliation: Manhattan Diagnostic Radiology, New York, NY, USA.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Saint Louis
authors.affiliation: New York University, School of Medicine, Center for Brain Health, New York, NY, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Randall
authors.affiliation: New York University, School of Medicine, Center for Brain Health, New York, NY, USA.
authors.forename: Tracy
authors.initials: T
authors.lastname: Butler
authors.affiliation: New York University, School of Medicine, Center for Brain Health, New York, NY, USA.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Xu
authors.affiliation: Pioneer BioSolutions Inc., Grayslake, IL, USA.
authors.forename: Raymond P
authors.initials: RP
authors.lastname: Zinkowski
authors.affiliation: Clinical Neurochemistry Lab, The Sahlgrenska Academy at University of Gothenburg, Mölndal Campus, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Fortea
authors.affiliation: New York University, School of Medicine, Center for Brain Health, New York, NY, USA.|New York University, School of Medicine, Department of Neurology, New York, NY, USA.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fossati
authors.affiliation: New York University, School of Medicine, Department of Neurology, New York, NY, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wisniewski
authors.affiliation: Litwin-Zucker Research Center, The Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Davies
authors.affiliation: Clinical Neurochemistry Lab, The Sahlgrenska Academy at University of Gothenburg, Mölndal Campus, Sweden.
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.affiliation: New York University, School of Medicine, Center for Brain Health, New York, NY, USA.|Steven and Alexandra Cohen NYU Center for Traumatic Brain Injury.
authors.forename: Mony J
authors.initials: MJ
authors.lastname: de Leon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D012372:ROC Curve; D012680:Sensitivity and Specificity; D016875:tau Proteins / Q000134:cerebrospinal fluid*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016875:tau Proteins
keywords: Alzheimer’s disease; P-tau181; P-tau231; biomarkers; hyperphosphorylated tau