Blood phosphorylated tau for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis.

We aimed to evaluate the diagnostic performance of plasma p-tau biomarkers and individual p-tau assays to identify biologically defined Alzheimer's disease.

我们的目标是评估血浆p-tau生物标志物及其个体p-tau检测的诊断性能，以识别生物学定义的阿尔茨海默病。

Methods

For this systematic reviewand meta-analysis, we searched Embase, MEDLINE, PubMed, Scopus, and Web of Science for articles published from July 1, 1984 up to Dec 9, 2024, that reported on the discriminative accuracy of plasma p-tau biomarkers for amyloid-PET, tau-PET, CSF, and neuropathological reference standards.

在这项系统评价和荟萃分析中，我们检索了Embase、MEDLINE、PubMed、Scopus和Web of Science数据库，查找了从1984年7月1日到2024年12月9日发表的有关血浆p-tau生物标志物对淀粉样蛋白PET、tau-PET、CSF和神经病理学参考标准的区分准确性报告的文章。

We included cohort, case-control, cross-sectional, and randomised controlled studies that recruited adults from any setting.

我们纳入了队列研究、病例对照研究、横断面研究和随机对照研究，这些研究招募了来自任何环境的成年人。

Articles were excluded if they did not contain data on a p-tau blood biomarker, did not contain an appropriate biological reference standard, did not report diagnostic accuracy data, included participants younger than 18 years, or reported duplicate or overlapping data from another publication.

如果文章不包含 p-tau 血液生物标志物的数据，没有适当的生物学参考标准，没有报告诊断准确性数据，包括年龄小于18岁的参与者，或者报告了来自另一篇出版物的重复或重叠数据，则将这些文章排除在外。

Summary data were independently extracted by eight authors.

摘要数据由八位作者独立提取。

Risk of bias was assessed using QUADAS-2.

使用QUADAS-2评估了偏倚风险。

The primary outcome was the diagnostic performance of plasma p-tau biomarkers for Alzheimer's disease.

主要结果是血浆p-tau生物标志物对阿尔茨海默病的诊断性能。

We used a bivariate random-effects meta-analysisto estimate pooled sensitivity, specificity, diagnostics odds ratio and area under the receiver operating characteristic curve.

我们使用双变量随机效应元分析来估计汇总的敏感性、特异性、诊断比值比和受试者工作特征曲线下面积。

We assessed the certainty of evidence using GRADE.

我们使用GRADE评估了证据的确定性。

This study was done following PRISMA-DTA guidelines and is registered with PROSPERO as CRD42023422143.

本研究遵循PRISMA-DTA指南，并已在PROSPERO注册，注册号为CRD42023422143。

Results

Of the 6429 studies identified by our search, 312 studies were assessed for eligibility, with 113 studies included in the final analysis, comprising 29 625 unique individuals.

我们的搜索共识别出6429项研究，其中312项研究被评估为符合资格，最终分析包括113项研究，涉及29625名独特个体。

Plasma p-tau217 was the highest-performing biomarker for identifying biologically defined Alzheimer's disease, with pooled sensitivity of 88·1% (95% CI 86·7-89·5, moderate certainty of evidence), specificity of 88·7% (87·4-89·9, moderate certainty of evidence), area under the receiver operating characteristic curve (AUROC) of 91·1% (88·9-92·4, moderate certainty of evidence), and diagnostic odds ratio of 50·7 (40·6-63·4). p-tau181 pooled sensitivity was 80·5% (78·4-82·4, low certainty of evidence), specificity was 76·4% (74·1-78·6, low certainty of evidence), AUROC was 81·5% (80·2-82·9, low certainty of evidence), and diagnostic odds ratio was 13·4 (11·4-16·7). p-tau205 pooled sensitivity was 76·6% (70·7-81·6, moderate certainty of evidence), specificity was 86·0% (78·6-91·2, moderate certainty of evidence), AUROC was 85·1% (80·7-89·6, moderate certainty of evidence), and diagnostic odds ratio was 20·2 (10·5-38·7). p-tau212 pooled sensitivity was 84·5% (75·5-90·6, moderate certainty of evidence), specificity was 87·3% (79·5-92·5, moderate certainty of evidence), AUROC was 90·3% (86·6-94·1, moderate certainty of evidence), and diagnostic odds ratio was 41·2 (22·0-77·3). p-tau231 pooled sensitivity was 75·2% (71·3-78·8, moderate certainty of evidence), specificity was 75·3% (71·2-78·9, moderate certainty of evidence), AUROC was 80·2 (77·6-82·7, moderate certainty of evidence), and diagnostic odds ratio was 9·3 (7·0-12·2).

血浆p-tau217是识别生物学定义的阿尔茨海默病的最佳生物标志物，其汇总敏感性为88.1%（95%置信区间86.7-89.5，证据确定性中等），特异性为88.7%（87.4-89.9，证据确定性中等），接收者操作特征曲线下面积（AUROC）为91.1%（88.9-92.4，证据确定性中等），诊断优势比为50.7（40.6-63.4）。

Approximately 90% of studies were rated as high risk of bias for not having used predefined or externally derived thresholds.

大约90%的研究被评为高偏倚风险，因为没有使用预先定义的或外部导出的阈值。

interpretation

Plasma p-tau217 is a highly sensitive and specific biomarker for Alzheimer's disease pathology, despite the high risk of bias of many studies.

尽管许多研究存在高风险偏倚，血浆p-tau217是阿尔茨海默病病理的高度敏感和特异性生物标志物。

Prospective clinical implementation studies in real-world settings are needed to characterise the effect of plasma p-tau217 on Alzheimer's disease diagnosis and clinical management.

需要在现实世界环境中进行前瞻性临床实施研究，以表征血浆p-tau217对阿尔茨海默病诊断和临床管理的影响。

funding

McGill Faculty of Medicine Fellowship.

麦吉尔大学医学院奖学金。