Association of Alzheimer's disease progression with YKL40 levels in peripheral blood and cerebrospinal fluid: a systematic review and meta-analysis.

INTRODUCTION: Chitinase 3-like protein 1 (CHI3L1 or YKL40) is a potential neuroinflammatory biomarker linked to the pathogenesis of Alzheimer's disease (AD). Previous studies have produced inconsistent results regarding YKL40 levels in various clinical stages of AD. This study aims to establish the correlation between YKL40 levels and AD progression through a meta-analysis of YKL40 levels in cerebrospinal fluid (CSF) and peripheral blood. METHODS: Comprehensive searches were conducted in PubMed, Medline, Web of Science, and the Cochrane Library to identify observational studies reporting CSF and peripheral blood YKL40 levels in AD patients, mild cognitive impairment (MCI) patients, preclinical AD (pre-AD) and healthy controls (HCs). A random effects meta-analysis was used to calculate the standardized mean difference (SMD) and 95% confidence intervals (CIs). RESULTS: Thirty observational studies involving 2,102 AD patients, 1,504 MCI patients, 118 pre-AD individuals, and 2,091 HCs were included. Significant differences in CSF YKL-40 levels were observed in AD vs. HC (SMD = 1.37, 95%CI: [1.09, 1.65]; DISCUSSION: Elevated YKL-40 levels in both CSF and peripheral blood are associated with the presence of Alzheimer's disease and its early stages, indicating that YKL-40 reflects neuroinflammatory processes involved in AD onset. While YKL-40 shows potential value for early identification along the AD continuum, its limited ability to differentiate between MCI and AD highlights the need for its combined use with other biomarkers in disease staging and progression assessment. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251031837.