{"id":"doi:10.1212/wnl.0000000000012727","kind":"article","title":"Comparing the Clinical Utility and Diagnostic Performance of CSF P-Tau181, P-Tau217, and P-Tau231 Assays","authors":["Leuzy A","Janelidze S","Mattsson-Carlgren N","Palmqvist S","Jacobs D","Cicognola C","Stomrud E","Vanmechelen E","Dage JL","Hansson O"],"author_count":10,"year":2021,"published":"2021-09-07","venue":"Neurology","cited_by":104,"doi":"10.1212/wnl.0000000000012727","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1212/wnl.0000000000012727","archive_url":"https://space-kitty.com/papers/doi:10.1212/wnl.0000000000012727","updated":null,"pmid":"34493616","pmcid":"PMC8605616","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC8605616/pdf","abstract":"Background and objectives Phosphorylated tau (p-tau) in CSF is considered an important biomarker in Alzheimer 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 β-amyloid (Aβ) and tau-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 A total of 629 participants in 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 2 commonly used assays (Innotest and Elecsys). Results Although 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 (area under the curve [AUC], 0.98 vs 0.88 [ p < 0.0001] - 0.96 [ p < 0.05]) and for identifying Aβ-PET (AUC, 0.86 vs 0.74 [ p < 0.0001] and 0.83 [ p < 0.001]) and tau-PET positivity (AUC, 0.94 vs 0.80-0.92, p < 0.0001). Finally, p-Tau181 Lilly generally performed better than the other p-tau181 assays (e.g., AD dementia vs non-AD, AUC, 0.96 vs 0.88 [p-tau181 Innotest ] and 0.89 [p-tau181 Elecsys ]; p < 0.0001). Discussion CSF p-tau217 Lilly seems to be more useful than other included p-tau assays in the workup of AD. Varied results across p-tau181 assays highlights the importance of anti-tau antibodies for biomarker performance. Classification of evidence This study provides Class II evidence that p-tau217 provides higher diagnostic accuracy for diagnosis of AD dementia than p-tau181 or p-tau231.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Comparing the Clinical Utility and Diagnostic Performance of CSF P-Tau181, P-Tau217, and P-Tau231 Assays\" by Leuzy A, Janelidze S, Mattsson-Carlgren N et al., https://doi.org/10.1212/wnl.0000000000012727, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"neurodegeneration","name":"Alzheimer's, Parkinson's & Neurodegeneration","domain_slug":"medicine"}],"cited_in_dossiers":[]}