Evaluation of Soluble Triggering Receptor Expressed on Myeloid Cells 2 ( <scp>sTREM2</scp> ) 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 (ρ = 0.32; p = 0.0012), although regression analysis indicated poor linearity. In contrast, serum and plasma sTREM2 levels were strongly correlated (ρ = 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 (ρ = 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.