Here, we examined the complex molecular landscape of the APOE region, harboring five genes (BCAM, NECTIN2, TOMM40, APOE, and APOC1) and represented by 30 single nucleotide polymorphisms (SNPs) available from common genotyping arrays, by performing the first reported large‐scale analysis of linkage disequilibrium (LD) structures in five cohorts comprising 2,673 AD‐affected and 16,246 unaffected individuals. This evidence concerns the gene APOE and Alzheimer disease.