Figure 2.

Baseline Aβ42, p-tau, t-tau in CSF, and PiB-PET and rate of change in soluble TREM2 in CSF in carriers of pathogenic variants

Each panel represents the estimated individual slopes extracted from the respective separate univariate linear mixed effects (LME) models, which assessed the association between the baseline predictor biomarker (Aβ42 in CSF [A], PiB-PET cortical uptake [B], t-tau in CSF [C], and p-tau in CSF [D]), and the subsequent longitudinal change in soluble TREM2 in CSF. β values and p values indicate the effect and statistical significance of the interaction term time from baseline × predictor-baseline-biomarker in each separate univariate LME model. The interaction term represents the effect of the baseline biomarker on the longitudinal change in soluble TREM2 in CSF. The separate univariate LME model is explained further in the appendix (p 13). Each univariate LME model consisted of longitudinal CSF soluble TREM2 as the dependent variable (ie, the outcome), time from-baseline, estimated years to symptom onset (EYO) at baseline, predictor biomarker at baseline and interactions Time × EYO at baseline and Time × Predictor at baseline as fixed factors and individual slope, intercept, and family cluster as random factors. Continuous red lines represent the association between the individual slopes, which were estimated from the univariate LME models and the baseline biomarker. Bands represent 95% CI. (A) Low baseline amounts of Aβ42 in CSF were associated with a subsequent augmented rate of change in soluble TREM2, according to the respective LME model. For total cortical PiB-PET uptake at baseline (B), baseline t-tau in CSF (C), and baseline p-tau in CSF (D), we did not find any significant effect on the subsequent rate of soluble TREM2 change estimated by the LME models (appendix p 13). PiB-PET=Pittsburgh compound B PET. p-tau=phosphorylated tau on threonine 181. SUVR=standardised uptake value ratio. t-tau=total tau.