Our comprehensive bioinformatics analysis highlights that the well-known gene APOE, which encodes the ligand in three dysregulated LR pairs, interacts with receptors encoded by LRP1, LRP6, and SORL1. The three dysregulated LR pairs were identified as downregulated in AD compared to controls in discovery and replication datasets (Fig. 2b, c). This evidence concerns the gene SORL1 and Alzheimer disease.