Technical and clinical validation of glial reactivity biomarkers sTREM2 and YKL-40 in Alzheimer’s disease

Abstract

Glial reactivity plays an important role in the pathogenesis of Alzheimer’s disease (AD). Biomarkers associated with this process have the potential for understanding AD pathogenesis and facilitating the development of novel therapeutic strategies. Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) and YKL-40, also known as chitinase 3-like protein 1 (CHI3L1), are involved in the modulation of these glial responses. Our study aimed to conduct both technical and clinical validation of an in-house Meso Scale Discovey (MSD) assay and a commercial enzyme-linked immunosorbent assay (ELISA) for quantifying these biomarkers in cerebrospinal fluid (CSF) of AD patients. Technical validation included spike recovery, parallelism and precision tests. Clinical validation involved investigating the biomarker correlations with demographic factors within the cohort and the differences between biologically diagnosed AD and non-AD patients. Both assays showed high accuracy, robustness, and consistency in measuring CSF sTREM2 and YKL-40. Both biomarkers increased with age and CSF YKL40 was higher in patients with biological defined AD. Additionally, significant correlations were observed between CSF sTREM2, YKL-40, and the core CSF biomarkers Aβ40, Aβ42, and pTau181. No significant associations were found between CSF sTREM2, YKL-40, sex, APOE ε4 profile and MMSE scores.