Plasma and CSF biomarkers in a memory clinic: Head‐to‐head comparison of phosphorylated tau immunoassays
Nicholas J. Ashton, Albert Puig‐Pijoan, Marta Milà‐Alomà, Aida Fernández‐Lebrero, Greta García‐Escobar, Fernando González‐Ortiz, Przemysław R. Kac, Wagner S. Brum, Andréa L. Benedet, Juan Lantero‐Rodriguez, Theresa A. Day, Jeroen Vanbrabant, Erik Stoops, Eugeen Vanmechelen, Gallen Triana‐Baltzer, Setareh Moughadam, Hartmuth C. Kolb, Paula Ortiz‐Romero, Thomas K. Karikari, Carolina Minguillón, Juan José Hernández Sánchez, Irene Navalpotro‐Gómez, Oriol Grau‐Rivera, R.M. Manero, Víctor Puente‐Periz, Rafael de la Torre, Jaume Roquer, Jeff L. Dage, Henrik Zetterberg, Kaj Blennow, Marc Suárez‐Calvet
Abstract
INTRODUCTION: Direct comparisons of the main blood phosphorylated tau immunoassays in memory clinic populations are needed to understand possible differences. METHODS: In the BIODEGMAR study, 197 participants presenting with cognitive complaints were classified into an Alzheimer's disease (AD) or a non-AD cerebrospinal fluid (CSF) profile group, according to their amyloid beta 42/ phosphorylated tau (Aβ42/p-tau) ratio. We performed a head-to-head comparison of nine plasma and nine CSF tau immunoassays and determined their accuracy to discriminate abnormal CSF Aβ42/p-tau ratio. RESULTS: All studied plasma tau biomarkers were significantly higher in the AD CSF profile group compared to the non-AD CSF profile group and significantly discriminated abnormal CSF Aβ42/p-tau ratio. For plasma p-tau biomarkers, the higher discrimination accuracy was shown by Janssen p-tau217 (r = 0.76; area under the curve [AUC] = 0.96), ADx p-tau181 (r = 0.73; AUC = 0.94), and Lilly p-tau217 (r = 0.73; AUC = 0.94). DISCUSSION: Several plasma p-tau biomarkers can be used in a specialized memory clinic as a stand-alone biomarker to detect biologically-defined AD. HIGHLIGHTS: Patients with an Alzheimer's disease cerebrospinal fluid (AD CSF) profile have higher plasma phosphorylated tau (p-tau) levels than the non-AD CSF profile group. All plasma p-tau biomarkers significantly discriminate patients with an AD CSF profile from the non-AD CSF profile group. Janssen p-tau217, ADx p-tau181, and Lilly p-tau217 in plasma show the highest accuracy to detect biologically defined AD. Janssen p-tau217, ADx p-tau181, Lilly p-tau217, Lilly p-tau181, and UGot p-tau231 in plasma show performances that are comparable to their CSF counterparts.