Estimation of blood-based biomarkers of glial activation related to neuroinflammation

BACKGROUND: Neuroinflammation is a well-known feature of Alzheimer’s disease (AD), and a blood-based test for estimating the levels of neuroinflammation would be expected. In this study, we examined and validated a model using blood-based biomarkers to predict the level of glial activation due to neuroinflammation, as estimated by (11)C-DPA-713 positron emission tomography (PET) imaging. METHODS: We included 15 patients with AD and 10 cognitively normal (CN) subjects. Stepwise backward deletion multiple regression analysis was used to determine the predictors of the TSPO-binding potential (BP(ND)) estimated by PET imaging. The independent variables were age, sex, diagnosis, apolipoprotein E4 positivity, body mass index and the serum concentration of blood-based biomarkers, including monocyte chemotactic protein 1 (MCP-1), fractalkine, chitinase 3-like protein-1 (CHI3L1), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and clusterin. RESULTS: Sex, diagnosis, and serum concentrations of MCP1 and sTREM2 were determined as predictors of TSPO-BP(ND) in the Braak1-3 area. The serum concentrations of MCP1 and sTREM2 correlated positively with TSPO-BP(ND). In a leave one out (LOO) cross-validation (CV) analysis, the model gave a LOO CV R(2) of 0.424, which indicated that this model can account for approximately 42.4% of the variance of brain TSPO-BP(ND.) CONCLUSIONS: We found that the model including serum MCP-1 and sTREM2 concentration and covariates of sex and diagnosis was the best for predicting brain TSPO-BP(ND). The detection of neuroinflammation in AD patients by blood-based biomarkers should be a sensitive and useful tool for making an early diagnosis and monitoring disease progression and treatment effectiveness.