Ruben Smith, Leslie Shaw, Sebastian Palmqvist, Niklas Mattsson-Carlgren, Gregory Klein, Matteo Tonietto, Clara Quijano-Rubio, Christopher M Rank, Myrto Andreadou, Samantha C Burnham, Erik Stomrud
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Although the use of cerebrospinal fluid (CSF) biomarkers as alternatives to amyloid-PET and tau-PET has been explored, no in vitro diagnostic-approved or commercial CSF biomarker assays are currently available for detecting tau pathology in clinical practice.</p><p><strong>Methods: </strong>In this study, we determined and validated the optimal cutoff value for the ratio of tau phosphorylated at a threonine residue at position 181 (pTau<sub>181</sub>) to β-amyloid(1-42) (Aβ<sub>42</sub>) in CSF, measured with the Elecsys<sup>®</sup> Phospho-Tau (181P) CSF and β-Amyloid(1-42) CSF immunoassays (Roche Diagnostics International Ltd, Rotkreuz, Switzerland), based on its concordance with binary tau-PET status. Clinical performance was explored using CSF measurements and tau-PET scans retrospectively obtained from a subset of subjects with mild cognitive impairment and dementia due to AD in two independent cohorts, Alzheimer's Disease Neuroimaging Initiative-2/3 (ADNI-2/3; N = 133) and Swedish BioFINDER-2 (N = 62).</p><p><strong>Results: </strong>In the first part of this analysis (ADNI-2/3 pre-analytics), a CSF pTau<sub>181</sub>/Aβ<sub>42</sub> cutoff value of 0.0395 was selected as the best compromise between positive percent agreement (PPA) and negative percent agreement (NPA) for the tau-PET visual read endpoint. After adjustment to account for differences between the ADNI-specific protocol and the manufacturer's recommended pre-analytical protocol used in BioFINDER-2, the optimal CSF pTau<sub>181</sub>/Aβ<sub>42</sub> cutoff value was set at 0.037. The adjusted cutoff was validated in BioFINDER-2 and was associated with a PPA of 85.7% (95% confidence interval [CI] 70.6, 93.7), NPA of 70.4% (95% CI 51.5, 84.1), and overall percent agreement (OPA) of 79.0% (95% CI 67.4, 87.3); the positive and negative likelihood ratios were 2.89 and 0.203, respectively.</p><p><strong>Conclusion: </strong>The Elecsys CSF pTau<sub>181</sub>/Aβ<sub>42</sub> ratio may be a reliable tool for identifying tau pathology in clinical practice.</p>","PeriodicalId":19216,"journal":{"name":"Neurology and Therapy","volume":" ","pages":"2011-2031"},"PeriodicalIF":4.8000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450182/pdf/","citationCount":"0","resultStr":"{\"title\":\"Clinical Performance of the Elecsys CSF pTau<sub>181</sub>/Aβ<sub>42</sub> Ratio for Concordance with Tau-PET in Two Independent Cohorts.\",\"authors\":\"Ruben Smith, Leslie Shaw, Sebastian Palmqvist, Niklas Mattsson-Carlgren, Gregory Klein, Matteo Tonietto, Clara Quijano-Rubio, Christopher M Rank, Myrto Andreadou, Samantha C Burnham, Erik Stomrud\",\"doi\":\"10.1007/s40120-025-00798-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Amyloid- and tau-positron emission tomography (PET) are promising modalities for detecting pathological changes associated with Alzheimer's disease (AD); however, their application is limited. 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引用次数: 0
摘要
淀粉样蛋白和tau正电子发射断层扫描（PET）是检测阿尔茨海默病（AD）相关病理变化的有希望的方式；然而，它们的应用是有限的。尽管已经探索了脑脊液（CSF）生物标志物作为淀粉样蛋白pet和tau- pet的替代品，但目前还没有体外诊断批准或商业化的脑脊液生物标志物检测方法可用于临床实践中检测tau病理。方法：在本研究中，我们确定并验证了脑脊液中苏氨酸位点181位磷酸化的tau蛋白（pTau181）与β-淀粉样蛋白（1-42）（a - β42）之比的最佳截止值，使用Elecsys®Phospho-Tau （181P）脑脊液和β-淀粉样蛋白（1-42）脑脊液免疫测定（罗氏诊断国际有限公司，Rotkreuz，瑞士），基于其与二元tau- pet状态的一致性。临床表现通过脑脊液测量和tau-PET扫描进行回顾性研究，这些扫描来自两个独立队列，阿尔茨海默病神经影像学倡议-2/3 (ADNI-2/3)；N = 133)和瑞典BioFINDER-2 （N = 62）。结果：在本分析的第一部分（ADNI-2/3预分析）中，CSF pTau181/ a β42的截止值为0.0395，被选为tau-PET视觉读取终点的阳性百分比一致性（PPA）和阴性百分比一致性（NPA）之间的最佳折衷。根据adni特异性方案与BioFINDER-2中使用的制造商推荐的分析前方案之间的差异进行调整后，最佳CSF pTau181/Aβ42截止值设置为0.037。调整后的截止值在BioFINDER-2中得到验证，PPA为85.7%(95%置信区间[CI] 70.6, 93.7)， NPA为70.4% (95% CI 51.5, 84.1)，总体百分比一致性（OPA）为79.0% (95% CI 67.4, 87.3)；正似然比为2.89，负似然比为0.203。结论：Elecsys脑脊液pTau181/ a - β42比值可作为临床诊断tau病理的可靠工具。
Clinical Performance of the Elecsys CSF pTau181/Aβ42 Ratio for Concordance with Tau-PET in Two Independent Cohorts.
Introduction: Amyloid- and tau-positron emission tomography (PET) are promising modalities for detecting pathological changes associated with Alzheimer's disease (AD); however, their application is limited. Although the use of cerebrospinal fluid (CSF) biomarkers as alternatives to amyloid-PET and tau-PET has been explored, no in vitro diagnostic-approved or commercial CSF biomarker assays are currently available for detecting tau pathology in clinical practice.
Methods: In this study, we determined and validated the optimal cutoff value for the ratio of tau phosphorylated at a threonine residue at position 181 (pTau181) to β-amyloid(1-42) (Aβ42) in CSF, measured with the Elecsys® Phospho-Tau (181P) CSF and β-Amyloid(1-42) CSF immunoassays (Roche Diagnostics International Ltd, Rotkreuz, Switzerland), based on its concordance with binary tau-PET status. Clinical performance was explored using CSF measurements and tau-PET scans retrospectively obtained from a subset of subjects with mild cognitive impairment and dementia due to AD in two independent cohorts, Alzheimer's Disease Neuroimaging Initiative-2/3 (ADNI-2/3; N = 133) and Swedish BioFINDER-2 (N = 62).
Results: In the first part of this analysis (ADNI-2/3 pre-analytics), a CSF pTau181/Aβ42 cutoff value of 0.0395 was selected as the best compromise between positive percent agreement (PPA) and negative percent agreement (NPA) for the tau-PET visual read endpoint. After adjustment to account for differences between the ADNI-specific protocol and the manufacturer's recommended pre-analytical protocol used in BioFINDER-2, the optimal CSF pTau181/Aβ42 cutoff value was set at 0.037. The adjusted cutoff was validated in BioFINDER-2 and was associated with a PPA of 85.7% (95% confidence interval [CI] 70.6, 93.7), NPA of 70.4% (95% CI 51.5, 84.1), and overall percent agreement (OPA) of 79.0% (95% CI 67.4, 87.3); the positive and negative likelihood ratios were 2.89 and 0.203, respectively.
Conclusion: The Elecsys CSF pTau181/Aβ42 ratio may be a reliable tool for identifying tau pathology in clinical practice.
期刊介绍：
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Neurology and Therapy aims to provide reliable and inclusive, rapid publication for all therapy related research for neurological indications, supporting the timely dissemination of research with a global reach, to help advance scientific discovery and support clinical practice.
Neurology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of neurological and psychiatric therapies, (also covering surgery and devices). Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed.
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