REVIEW article
Front. Neurol.
Sec. Neurological Biomarkers
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1667402
This article is part of the Research TopicIdentification of Neurological Biomarkers for Neurodegenerative DisordersView all 3 articles
Evaluation of the Diagnostic Efficacy of Core Biomarkers in Cerebrospinal Fluid for Alzheimer's Disease: A Systematic Review and Meta-Analysis
Provisionally accepted
- Jinan University, Guangzhou, China
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Objective: Core cerebrospinal fluid (CSF) biomarkers serve as pivotal diagnostic indicators for Alzheimer's disease, yet their diagnostic efficacy varies substantially across different markers. This study employs a Bayesian meta-analytic approach to comprehensively evaluate the diagnostic accuracy of individual core CSF biomarkers for Alzheimer's disease (AD). Methods: A comprehensive literature search was conducted in Web of Science, PubMed, and other databases for English-language studies published between January 2013 and April 2025. Following predefined inclusion/exclusion criteria, eligible studies were selected for methodological quality assessment using standardized tools. Data extraction was subsequently performed, and statistical analyses were conducted using Meta-DiSc 1.4, Stata 15.1, and R 4.3.2 software packages. Results: This meta-analysis systematically evaluated the diagnostic value of eight core CSF biomarkers for AD, incorporating 23 eligible studies (2,187 AD cases and 2,019 non-AD). Key findings revealed: (1) Among individual biomarkers, p-tau217 demonstrated superior diagnostic performance, with sensitivity of 0.95 (95% CI: 0.92-0.97), specificity of 0.94 (95% CI: 0.88-0.98), area under the curve (AUC) of 0.99 (95% CI: 0.97-1.00), and an exceptionally high diagnostic odds ratio (DOR) of 395.28 (95% CI: 92.17-1,305.79), all parameters being significantly better than other biomarkers (P<0.001). Both p-tau231 (AUC=0.97) and p-tau181 (AUC=0.90) also exhibited commendable diagnostic accuracy. (2) For biomarker ratios, the Aβ42/p-tau181 ratio showed optimal overall diagnostic efficacy, with sensitivity of 0.90 (95% CI: 0.86-0.94) and AUC of 0.93 (95% CI: 0.90-0.96), significantly outperforming other ratio combinations (P<0.05). Conclusion:This study demonstrates that among core CSF biomarkers for AD, p-tau217 exhibits the most outstanding diagnostic performance as a standalone biomarker, while the Aβ42/p-tau181 ratio shows superior diagnostic efficacy among biomarker combinations. Based on current evidence-based medical data, we recommend the combined use of p-tau217 and Aβ42/p-tau181 ratio as first-line core CSF biomarker panel for AD diagnosis, providing reliable laboratory evidence for early screening and differential diagnosis of AD in clinical practice.
Keywords: Bayesian meta-analysis, Alzheimer's disease, Core cerebrospinal Fluid Biomarkers, β-amyloid protein, tau protein, Diagnostic Performance Evaluation
Received: 25 Jul 2025; Accepted: 21 Aug 2025.
Copyright: © 2025 Baohua, Yangtai, Yiyang, Zhuang, Li and lihui. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Ma Li, Jinan University, Guangzhou, China
cao lihui, Jinan University, Guangzhou, China
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