Fig. 4

sTREM2 mediates early synaptic loss. A–E Odds ratio (OR) analysis of [18F]MK6240 SUVR Braak I-V (A), neocortical [¹⁸F]AZD4694 SUVR (B), plasma GFAP (C), whole brain [¹¹C]PBR28 SUVR (D) and CSF sTREM2 (E) in T-N- participants and across the whole continuum. ORs, 5% and 95% confidence intervals are displayed corrected for covariates (sex, age, educational years, APOE ε4 status) or covariates and respective other biomarkers for tau load, amyloid load, astrogliosis and microglial activation. F and G Structural equation models of CSF sTREM2 and plasma GFAP with 14-3-3 \(\upzeta /\updelta\) in T-N-participants (F) and across the AD continuum (G). [18F]MK6240 SUVR Braak I–V and [¹⁸F]AZD4694 SUVR were tested as mediators. Goodness-of-fit indicators are provided in Additional file 1: Table S3. Black lines show direct effects, green lines show GFAP-mediated effects, blue lines show sTREM2-mediated effects, solid lines show significant and dashed lines show not significant effects. Standardized estimates are provided in the figure. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001