Fig. 3: Genetic influences on meta-temporal tau.

Lines show the estimated marginal levels of meta-temporal tau (TauMeta) pathology for individuals with varying genetic profiles at different levels of entorhinal cortex tau (TauEC), with amyloid beta (Aβ) fixed at 40 centiloids to facilitate comparison. Different effects in the discovery sample (n = 626) for (a) Apolipoprotein E (APOE)-ε4, (b) Triggering Receptor Expressed on Myeloid Cells 2 (TREM2), and c. their interaction. Different effects in the replication sample (n = 726) for (d) APOE-ε4. e Causal path model to estimate TauMeta. Solid lines indicate a direct effect of an upstream variable on a downstream pathology, dashed lines indicate an interactive effect between upstream variables (i.e. Aβ, TauEC, or genetic variable) on meta-temporal tau. Lines initiating from the black genetic variables box may indicate a direct or interactive effect of genetic variables on the outcome variable. Values in the parentheses indicate level of genetic variable (APOE-ε4 alleles (0,1,2) and TREM2 risk variant carrier status (0,1)). Source data are provided as a Source Data file.