Notably, the effects of APOE ε4 genotype on the plasma proteome were so robust that a machine learning model with only five proteins (SPC25, NEFL, S100A13, TBCA and LRRN1) predicted APOE ε4 carrier status in unseen patients with high accuracy, both within AD and within non-AD Patients (area under the curve (AUC) range, 0.90–0.96; Fig. 3d). This evidence concerns the gene NEFL and Alzheimer disease.