Protective and risk effects of Apolipoprotein E variants on Alzheimer’s disease in Latin America : a systematic review and meta-analysis

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Orellana, Paulina and Caviedes, Ariel and Gonzalez, Liset and Ochoa-Rosales, Carolina and Gonzalez-Silva, Carolina and Hernandez, Hernan and Britton, Gabrielle B. and Villarreal, Alcibiades E. and Campos, Victoria and Hendrie, Hugh and Acosta-Uribe, Juliana and Pina-Escudero, Stefanie D. and Yokoyama, Jennifer S. and Parra, Mario and Santamaria-Garcia, Hernando and Ibáñez, Agustín and de la Cruz, Rolando and Duran-Aniotz, Claudia (2026) Protective and risk effects of Apolipoprotein E variants on Alzheimer’s disease in Latin America : a systematic review and meta-analysis. Alzheimer's & Dementia: The Journal of the Alzheimer's Association. ISSN 1552-5279 (In Press)

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Abstract

The 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 3,206 AD and 5,515 controls. The ε4 allele demonstrated significant association with increased AD risk (OR = 3.25, 95% CI [2.82–3.76]), while ε3 showed protective effects (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.

ORCID iDs

Orellana, Paulina, Caviedes, Ariel, Gonzalez, Liset, Ochoa-Rosales, Carolina, Gonzalez-Silva, Carolina, Hernandez, Hernan, Britton, Gabrielle B., Villarreal, Alcibiades E., Campos, Victoria, Hendrie, Hugh, Acosta-Uribe, Juliana, Pina-Escudero, Stefanie D., Yokoyama, Jennifer S., Parra, Mario ORCID logoORCID: https://orcid.org/0000-0002-2412-648X, Santamaria-Garcia, Hernando, Ibáñez, Agustín, de la Cruz, Rolando and Duran-Aniotz, Claudia;
CORE (COnnecting REpositories)