Authors: Orellana, P., Caviedes, A., Gonzalez, L., Ochoa-Rosales, C., Carmona, D., González-Silva, C., Hernández, H., Britton, G. B., Villarreal, A. E., Campos, V., Hendrie, H., Acosta-Uribe, J., Pina-Escudero, S. D., Yokoyama, J. S., Vilor-Tejedor, N., Parra, M., Santamaria-García, H., Ibañez, A., de la Cruz, R., & Duran-Aniotz, C.

Abstract: The apolipoprotein E (APOE) ε4 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 ε4 allele demonstrated significant association with increased AD risk (odds ratio [OR] = 3.25, 95% confidence interval [2.82–3.76]), while ε3 showed lower odds (0.42, [0.37–0.48]). Homozygous ε4/ε4 carriers had elevated risk (6.84, [5.09–9.19]), and heterozygous ε3/ε4 carriers showed moderate risk (2.59, [2.31–2.91]). Country-level analyses revealed variability, with Ecuador showing the highest OR for ε4/ε4 (13.29, [1.56–113.4]). These results confirm APOE ε4 as a major AD risk factor in LAC populations and highlight regional differences relevant to precision medicine.