Evaluation of the diagnostic efficacy of core biomarkers in cerebrospinal fluid for Alzheimer's disease: a systematic review and meta-analysis.

Abstract

<h4>Objective</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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 (<i>p</i> < 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 (<i>p</i> < 0.05).<h4>Conclusion</h4>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.