Causal mediation analysis results for the model investigating the relationships among amyloid group (A), tau in the ITG, and neurodegeneration in the ITG. The effect of amyloid on ITG CBF (in BLSA) and on ITG volume (in ADNI) was mediated via ITG tau. Arrows from A to ITG tau and from ITG tau to ITG CBF indicate the linear regression coefficients for these associations. 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.