Peripheral Blood and Cerebrospinal Fluid Levels of YKL-40 in Alzheimer’s Disease: A Systematic Review and Meta-Analysis

The pathogenesis associated with Alzheimer’s disease (AD) is particularly complicated, and early diagnosis and course monitoring of the disease are not ideal based on the available core biomarkers. As a biomarker closely related to neuroinflammation, YKL-40 provides a potential scalable approach in AD, but its association remains controversial and inconclusive with AD. We conducted this study to assess the utility of YKL-40 levels in peripheral blood and cerebrospinal fluid (CSF) of AD patients and healthy controls (HCs) by meta-analysis. We systematically searched and screened relevant trials for comparing YKL-40 levels between AD patients and HCs in PubMed, Embase, Cochrane, and Web of Science, with a search deadline of 14 March 2023 for each database. A total of 17 eligible and relevant studies involving 1811 subjects, including 949 AD patients and 862 HCs, were included. The results showed that YKL-40 levels in the peripheral blood of AD patients and HCs did not possess significant differences. Subgroup analysis showed YKL-40 significantly differed in plasma (SMD = 0.527, 95%CI: [0.302, 0.752]; p = 0.000), but did not in serum. In the case of comparison with HCs, YKL-40 was significantly higher in CSF of AD patients (SMD = 0.893, 95%CI: [0.665, 1.121]; p = 0.000). Besides that, when we performed a combined analysis of total YKL-40 in both peripheral blood and CSF, overall YKL-40 concentrations were also significantly increased among AD patients (SMD = 0.608, 95%CI: [0.272, 0.943]; p = 0.000). YKL-40 provides support and rationale for the neuroinflammatory pathogenesis of AD. The significance of CSF levels of YKL-40 for early screening of AD is definite. Plasma levels of YKL-40 also appear to assist in discriminating AD patients from HCs, which facilitates early screening and monitoring of the natural course of AD.