Evaluation of Soluble Triggering Receptor Expressed on Myeloid Cells 2 (sTREM2) in Cerebrospinal Fluid, Serum, and Plasma Using the Fully Automated Lumipulse Platform

Background In this study, we first evaluated the relationship between sTREM2 concentrations in CSF, serum, and plasma of Alzheimer's disease (AD) patients using the newly developed Lumipulse G sTREM2 assay. Methods sTREM2 was measured by the fully automated Lumipulse G1200 platform (Fujirebio). Associations and agreement between matrices were assessed using Passing-Bablok regression, Spearman correlation, and Bland-Altman analyses. Sub-analyses explored the influence of disease stage and tau pathology. Results Median sTREM2 concentrations were highest in CSF, followed by serum and plasma. Serum and CSF sTREM2 levels showed a moderate but significant correlation (rho = 0.32; p = 0.0012), although regression analysis indicated poor linearity. In contrast, serum and plasma sTREM2 levels were strongly correlated (rho = 0.74; p < 0.001). The association between CSF and serum sTREM2 levels was independent of total and phosphorylated tau. Notably, a strong CSF-serum correlation was observed in the MCI due to AD group (rho = 0.74) but was completely lost in overt AD dementia, demonstrating a clear disease stage-dependent relationship. Conclusion CSF and blood sTREM2 capture partly distinct biological processes and show limited overall agreement. While serum and plasma sTREM2 are closely related, they are not interchangeable.