Background: The Apolipoprotein E ( APOE ) gene is the main risk factor for late-onset Alzheimer disease (LOAD). Genetic variants and haplotypes in regions near the APOE locus may be associated with LOAD in the Colombian population. Objective: We evaluated frequencies and risk of genetic variants and haplotypes in APOE , TOMM40 , and APOC1 promoters, also in putative regulatory enhancer elements ( TOMM40 IVS2-4 and TOMM40 IVS6) , and in cis-regulatory elements ( ME1 and BCR). Materials and Methods: Our case-control association study was carried out in 50 patients with LOAD and 50 controls. We determined frequencies and odd ratios for genetic variants and haplotypes. Results: We found a significant association between LOAD and genetic variants at the TOMM40 promoter, at TOMM40 IVS2-4 and TOMM40 IVS6 regulatory enhancer elements, and at the APOC1 promoter. Particularly, variants of Poly-T and APOC1 promoter could anticipate the age of onset of LOAD in our population. We identified three risk haplotypes in TOMM40 ( ACGGAG, ACGGGG, and ATAGGC) related to LOAD’s age of onset. We also found other risk or protection haplotypes at the TOMM40 and APOE promoters, at TOMM40 IVS2-4 , TOMM40 IVS6 regulatory enhancer elements, and at ME1. Conclusion: Genetic variants and haplotypes near the APOE locus are related to LOAD risk and accelerated onset of LOAD in the Colombian population.