We evaluated cerebrospinal fluid (CSF) levels of soluble Triggering receptor expressed on myeloid cells 2 (sTREM2) in the context of inflammatory changes in Alzheimer’s disease (AD) to better understand its role.

Inflammatory pathways may regulate Alzheimer’s disease progression. TREM2 rare protein coding genetic variants have been linked to AD. TREM2 is a microglial receptor involved in innate immunity.  There is still limited information about its functional role in the context of inflammatory changes among clinical AD patients. 

CSF total-tau and phosphorylated-tau levels did not correlate with CSF sTREM2 levels. CSF sTREM2 levels correlated with Vascular cell adhesion protein 1,VCAM1 (r=0.53, P=0.0001, FDR=0.01). In a network analysis the following analytes taken together also correlated with sTREM2: CRP, FGA, MMP3, TNFRSF1B, VCAM1    (r=0.577    p=1.100e-03). Network analysis also revealed Aβ42 correlates with sTREM 2 only when taken together with other inflammatory analytes(α1antitrypsin, CRP, F7, ENO2, CCL5,VEGFA,GC).  In a linear regression model with sTREM2 level as a dependent variable and CSF Aβ42, total-tau, significant inflammatory analytes from above and baseline MMSE as independent variables, only VACM1 was a significant predictor (β=0.04, p=0.04) of sTREM2 level.

VCAM1 which plays a role in leukocyte-endothelial cell adhesion and leukocyte migration from the blood into tissues best predicts CSF sTREM levels in MCI-AD.Understanding the role for sTREM2/VCAM1 is important in the context of developing novel immunomodulatory therapies in AD.