Here, we employ a trajectory modelling approach based on machine learning37 to quantify the multivariate relationships between key biomarkers (Aβ, tau, medial temporal atrophy)—in line with the biological framework of AD—and APOE 4 (4 allele of the Apolipoprotein E gene) genotype, the major genetic risk factor for late onset AD38. The gene discussed is APOE; the disease is Alzheimer disease.