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Plasma and CSF biomarkers in a memory clinic: Head-to-head comparison of phosphorylated tau immunoassays

Ashton NJ, Puig-Pijoan A, Milà-Alomà M, Fernández-Lebrero A, García-Escobar G, González-Ortiz F, Kac PR, Brum WS, Benedet AL, Lantero-Rodriguez J, Day TA, Vanbrabant J, Stoops E, Vanmechelen E, Triana-Baltzer G, Moughadam S, Kolb H, Ortiz-Romero P, Karikari TK, Minguillon C, Hernández Sánchez JJ, Navalpotro-Gómez I, Grau-Rivera O, María Manero R, Puente-Periz V, de la Torre R, Roquer J, Dage JL, Zetterberg H, Blennow K, Suárez-Calvet M

Abstracto

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.

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Reference

Ashton NJ, Puig-Pijoan A, Milà-Alomà M, Fernández-Lebrero A, García-Escobar G, González-Ortiz F, Kac PR, Brum WS, Benedet AL, Lantero-Rodriguez J, Day TA, Vanbrabant J, Stoops E, Vanmechelen E, Triana-Baltzer G, Moughadam S, Kolb H, Ortiz-Romero P, Karikari TK, Minguillon C, Hernández Sánchez JJ, Navalpotro-Gómez I, Grau-Rivera O, María Manero R, Puente-Periz V, de la Torre R, Roquer J, Dage JL, Zetterberg H, Blennow K, Suárez-Calvet M. Plasma and CSF biomarkers in a memory clinic: Head-to-head comparison of phosphorylated tau immunoassays. Alzheimers Dement. 2022 Nov 12. doi: 10.1002/alz.12841. Epub ahead of print. PMID: 36370462.