Chao Yuan, Hui Zhang, Xudong Chen, Lin Zhu, Zhonghao Wang, Yanping Wang, Shun Ge
For amyloid pathology, all technical platforms showed good diagnostic accuracy. While LC-MS/MS demonstrated the highest specificity, ECLIA demonstrated the maximum sensitivity. Its application in clinical practice is supported by the fact that the p-tau217/Aβ42 ratio performed much better than p-tau217 alone.
OBJECTIVE: To systematically evaluate the diagnostic accuracy of plasma phosphorylated tau 217 (p-tau217) for detecting amyloid pathology in Alzheimer's disease (AD), compare performance across different technical platforms, and assess the incremental diagnostic value of the p-tau217/Aβ42 ratio relative to single p-tau217 measurements.
METHODS: In order to find diagnostic accuracy studies of plasma p-tau217 utilizing amyloid positron emission tomography (PET) as the reference standard, we conducted a systematic search of PubMed and EMBASE between January 2020 and February 2026. Random-effects models were used to compute pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Technical platforms such as single-molecule array (Simoa), chemiluminescence immunoassay (CLIA), electrochemiluminescence immunoassay (ECLIA), and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to stratify subgroup studies. Studies that reported both p-tau217 alone and p-tau217/Aβ42 ratios were subjected to paired meta-analyses.This systematic review was registered with PROSPERO (registration number: CRD420261371940).
RESULTS: Included were 25 studies with 18,073 participants. Platform-specific pooled diagnostic accuracy estimates were as follows: Simoa had sensitivity of 0.894 (95% CI 0.861-0.920) and specificity of 0.875 (0.845-0.900); CLIA had sensitivity of 0.886 (0.860-0.907) and specificity of 0.865 (0.826-0.896); ECLIA had the highest sensitivity of 0.933 (95% CI 0.918-0.946) but lower specificity (0.791, 95% CI 0.571-0.915); LC-MS/MS showed sensitivity of 0.827 (95% CI 0.725-0.897) and the highest specificity of 0.938 (95% CI 0.692-0.990).There was significant variation between the studies (I2 = 63%-86%). The p-tau217/Aβ42 ratio approximately doubled the diagnostic odds ratio compared with p-tau217 alone (relative DOR 1.96, 95% CI 1.19-3.23), with mean sensitivity improvements of 3.6% and varying specificity changes (mean + 1.7%), according to paired meta-analyses of five studies.
CONCLUSIONS: For amyloid pathology, all technical platforms showed good diagnostic accuracy. While LC-MS/MS demonstrated the highest specificity, ECLIA demonstrated the maximum sensitivity. Its application in clinical practice is supported by the fact that the p-tau217/Aβ42 ratio performed much better than p-tau217 alone.