Abstract

The apolipoprotein E (APOE) epsilon 4 allele represents the strongest genetic risk factor for Alzheimer's disease (AD), but its role in genetically diverse Latin American and Caribbean (LAC) populations is underexplored. We conducted a meta-analysis of 35 studies from 11 LAC countries, encompassing 3206 patients with AD and 5515 controls. The epsilon 4 allele demonstrated significant association with increased AD risk (odds ratio [OR] = 3.25, 95% confidence interval [2.82-3.76]), while epsilon 3 showed lower odds (0.42, [0.37-0.48]). Homozygous epsilon 4/epsilon 4 carriers had elevated risk (6.84, [5.09-9.19]), and heterozygous epsilon 3/epsilon 4 carriers showed moderate risk (2.59, [2.31-2.91]). Country-level analyses revealed variability, with Ecuador showing the highest OR for epsilon 4/epsilon 4 (13.29, [1.56-113.4]). These results confirm APOE epsilon 4 as a major AD risk factor in LAC populations and highlight regional differences relevant to precision medicine.