Deconvolving Cerebrospinal Fluid Soluble TREM2 Signal and Longitudinal Associations with Cognition

Cerebrospinal fluid (CSF) soluble triggering receptor expressed on myeloid cells‐2 (sTREM2) is an emerging biomarker of neuroinflammation in Alzheimer’s disease (AD). Yet, sTREM2 expression has not been systematically evaluated in relation to concomitant drivers of neuroinflammation. We previously found a novel association between high Aβ40 (but not Aβ42) and high sTREM2 levels at baseline and replicated additional associations between a fluid biomarker of blood‐brain barrier (BBB) integrity and CSF biomarkers of neurodegeneration. Therefore, we sought to determine the relative contributions of these biological correlates to CSF sTREM2 levels during the prodromal stages of AD. Additionally we investigated whether the residual variance in sTREM2 level correlated with each biomarker predicted future cognitive performance.