Comparing the clinical utility and diagnostic performance of cerebrospinal fluid P-tau181, P-tau217 and P-tau231 assays

Leuzy, Antoine, Lund University, https://orcid.org/0000-0003-4542-7879

Janelidze, Shorena, Lund University

Mattsson-Carlgren, Niklas, Lund University

Palmqvist, Sebastian, Lund University

Jacobs, Dirk, ADx NeuroSciences

Cicognola, Claudia, Lund University

Stomrud, Erik, Lund University

Hansson, Oskar, Lund University

Vanmechelen, Eugeen, ADx NeuroSciences

Dage, Jeffrey, Eli Lilly and Company

antoine.leuzy@med.lu.se

Published Jun 15, 2021 on Dryad. https://doi.org/10.5061/dryad.4f4qrfjc7

Cite this dataset

Leuzy, Antoine et al. (2021). Comparing the clinical utility and diagnostic performance of cerebrospinal fluid P-tau181, P-tau217 and P-tau231 assays [Dataset]. Dryad. https://doi.org/10.5061/dryad.4f4qrfjc7

Abstract

Background and Objectives: Phosphorylated tau (P-tau) in cerebrospinal fluid (CSF) is considered an important biomarker in Alzheimer’s disease (AD) and has been incorporated in recent diagnostic criteria. Several variants exist, including P-tau at threonines 181 (P-tau181), 217 (P-tau217) and 231 (P-tau231). However, no studies have compared their diagnostic performance or association to amyloid-β (Aβ) and Tau positron emission tomography (PET). Understanding which P-tau variant to use remains an important yet answered question. We aimed to compare the diagnostic accuracy of P-tau181, P-tau217 and P-tau231 in CSF for AD and their association with Aβ and Tau-PET.

Methods: 629 subjects from the Swedish BioFINDER-2 study were included (cognitively unimpaired, n=334; Aβ-positive mild cognitive impairment, n=84; AD dementia, n=119; and non-AD disorders, n=92). In addition to P-tau181 and P-tau217 measured using assays with the same detector antibodies from Eli Lilly (P-tau181_Lilly, P-tau217_Lilly) and P-tau231, we also included P-tau181 measurements from two commonly used assays (Innotest and Elecsys).

Results: Though all P-tau variants increased across the AD continuum, P-tau217_Lilly showed the greatest dynamic range (13-fold-increase vs 1.9-5.4-fold-increase for other P-tau variants for AD dementia vs non-AD). P-tau217_Lilly showed stronger correlations with Aβ- and Tau-PET (P<0.0001). P-tau217_Lilly exhibited higher accuracy than other P-tau variants for separating AD dementia from non-AD (AUC, 0.991vs 0.906-0.982, P<0.0001) and for identifying Aβ- (AUC, 0.951 vs 0.816-0.924, P<0.0001) and Tau-PET positivity (AUC, 0.957 vs 0.836-0.938, P<0.0001). Finally, P-tau181_Lillygenerally performed better than the other P-tau₁₈₁ assays, (e.g., AD dementia vs non-AD, AUC, 0.976 vs 0.923, P<0.0001).

Discussion: CSF P-tau217_Lilly seem to be more useful than other included P-tau assays in the work-up of AD. Varied results across P-tau181 assays also highlights the importance of anti-tau antibodies for biomarker performance.

Classification of evidence: This study provides class II evidence that phosphorylated tau at threonine 217 provides higher diagnostic accuracy for diagnosis of AD dementia than P-tau at threonine 181 or 231.