Fig. 4: Direct, mediation and total effects of upstream pathology on tau for different levels of sex, APOE-ε4, and TREM2 risk carrier status. | Nature Communications

Fig. 4: Direct, mediation and total effects of upstream pathology on tau for different levels of sex, APOE-ε4, and TREM2 risk carrier status.

From: Variable and interactive effects of Sex, APOE ε4 and TREM2 on the deposition of tau in entorhinal and neocortical regions

Fig. 4

Estimated effects along the amyloid beta (Aβ) → entorhinal cortex tau (TauEC) → meta-temporal tau (TauMeta) cascade are shown for contrasts defined by Apolipoprotein E (APOE)-ε4 alleles (0,1,2), Sex (female, male), and Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) risk variant carrier status (0,1). The top row (a–d) shows results from the discovery sample (n = 626), and the bottom row (e–h) shows results from the replication sample (n = 726). Panels (a) and (e) show the direct effect from Aβ to TauEC; panels (b) and (f) show the direct effect from TauEC to TauMeta; panels (c) and (g) show the mediation effect of Aβ on TauMeta via TauEC; and panels (d) and (h) show the total effect of Aβ on TauMeta. Each point represents the estimated effect contrast between two levels (e.g., APOE-ε4(2) - APOE-ε4(0) corresponds to the effect estimate for APOE-ε4 homozygotes minus that for non-carriers), and error bars indicate confidence intervals derived from 1000 multiplier bootstrapped samples: 95% two-sided for the discovery sample (a–d), and 95% one-sided (5th to 100th percentile) for validation in the replication sample (e–h). Source data are provided as a Source Data file.

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