FIGURE 7.

Tau neocortical progression is influenced by synergistic interaction of medial temporal lobe amyloid and tau. (A), Schematic of relationship among amyloid, medial temporal lobe tau, neocortical tau, and neurodegeneration. (B), Causal mediation analysis results for the model investigating the relationships among amyloid groups (+/–) and tau in the EC and the ITG in the BLSA and ADNI. The effect of amyloid on ITG tau is mediated by EC tau. Arrow from A to EC tau indicates the linear regression coefficient, and the gray and red arrows from EC tau to ITG tau indicate the linear regression coefficients for the amyloid negative and positive groups, respectively. Both the mediator and the outcome models were adjusted for age, sex, APOE ε4 positivity, years of education, and 10‐year cardiovascular disease risk. ***P < 0.001, **P < 0.01, *P < 0.05. A, amyloid; ACME, average causal mediation effect; ADNI, Alzheimer's Disease Neuroimaging Initiative; APOE, apolipoprotein E; BLSA, Baltimore Longitudinal Study of Aging; EC, entorhinal cortex; ITG, inferior temporal gyrus. Reproduced from Bilgel et al. ²¹⁷