Greater Specificity for Cerebrospinal Fluid P-tau231 over P-tau181 in the Differentiation of Healthy Controls from Alzheimer’s Disease

Article type: Research Article

Authors: Spiegel, Jonathan^{a; b} | Pirraglia, Elizabeth^a | Osorio, Ricardo S.^a | Glodzik, Lidia^a | Li, Yi^a | Tsui, Wai^a | Saint Louis, Leslie A.^c | Randall, Catherine^a | Butler, Tracy^a | Xu, Jinfeng^a | Zinkowski, Raymond P.^d | Zetterberg, Henrik^e | Fortea, Juan^f | Fossati, Silvia^{a; g} | Wisniewski, Thomas^g | Davies, Peter^h | Blennow, Kaj^e | de Leon, Mony J.^{a; i; *}

Affiliations: [a] New York University, School of Medicine, Center for Brain Health, New York, NY, USA | [b] Wellington C. Mepham High School, Bellmore, NY, USA | [c] Manhattan Diagnostic Radiology, New York, NY, USA | [d] Pioneer BioSolutions Inc., Grayslake, IL, USA | [e] Clinical Neurochemistry Lab, The Sahlgrenska Academy at University of Gothenburg, Mölndal Campus, Sweden | [f] Department of Neurology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain | [g] New York University, School of Medicine, Department of Neurology, New York, NY, USA | [h] Litwin-Zucker Research Center, The Feinstein Institute for Medical Research, Manhasset, NY, USA | [i] Steven and Alexandra Cohen NYU Center for Traumatic Brain Injury

Correspondence: [*] Correspondence to: Dr. Mony de Leon, NYU School of Medicine, Department of Psychiatry, Center for Brain Health, 145 E. 32 Street, New York, NY 10016, USA. Tel.: +1 212 263 5805; E-mail: [email protected]

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.

Keywords: Alzheimer’s disease, biomarkers, hyperphosphorylated tau, P-tau181, P-tau231

DOI: 10.3233/JAD-150167

Journal: Journal of Alzheimer's Disease, vol. 49, no. 1, pp. 93-100, 2016