Association of apolipoprotein E variants on Alzheimer's disease in Latin America: A systematic review and meta-analysis

Paulina Orellana; Ariel Caviedes; Liset Gonzalez; Carolina Ochoa-Rosales; Danilo Carmona; Carolina González-Silva; Hernán Hernández; Gabrielle B. Britton; Alcibiades E. Villarreal; Victoria Campos; Hugh Hendrie; Juliana Acosta-Uribe; Stefanie D. Pina-Escudero; Jennifer S. Yokoyama; Natalia Vilor-Tejedor; Mario Parra; Hernando Santamaria-García; Agustín Ibañez; Rolando de la Cruz; Claudia Duran-Aniotz

doi:10.1002/alz.71224

Association of apolipoprotein E variants on Alzheimer's disease in Latin America: A systematic review and meta-analysis

Paulina Orellana
, Ariel Caviedes
, Liset Gonzalez
, Carolina Ochoa-Rosales
, Danilo Carmona
, Carolina González-Silva
, Hernán Hernández
, Gabrielle B. Britton
, Alcibiades E. Villarreal
, Victoria Campos
, Hugh Hendrie
, Juliana Acosta-Uribe
, Stefanie D. Pina-Escudero
, Jennifer S. Yokoyama
, Natalia Vilor-Tejedor
, Mario Parra
, Hernando Santamaria-García
, Agustín Ibañez
, Rolando de la Cruz
, Claudia Duran-Aniotz

Universidad Adolfo Ibáñez
Radboud University Nijmegen
Instituto de Investigaciones Científicas y Servicios de Alta Tecnología de Panamá
Instituto Nacional de Neurologia y Neurocirugia
Indiana University
Universidad de Antioquia
University of California at Santa Barbara
University of California at San Francisco
Trinity College Dublin
Utrecht University
Pasqual Maragall Foundation
University of Strathclyde
Hospital Universitario San Ignacio
Universidad de San Andrés
Istanbul Medipol University

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	e71224
Number of pages	15
Journal	Alzheimer's and Dementia
Volume	22
Issue number	2
DOIs	https://doi.org/10.1002/alz.71224
State	Published - 01 Feb 2026

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Alzheimer's disease
Caribbean
Latin America
genetic risk factors
meta-analysis
systematic review

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10.1002/alz.71224

Cite this

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. (2026). Association of apolipoprotein E variants on Alzheimer's disease in Latin America: A systematic review and meta-analysis. Alzheimer's and Dementia, 22(2), Article e71224. https://doi.org/10.1002/alz.71224

@article{b301efc35bf64ce4ac4aff043d47cc16,

title = "Association of apolipoprotein E variants on Alzheimer's disease in Latin America: A systematic review and meta-analysis",

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.",

keywords = "Alzheimer's disease, Caribbean, Latin America, genetic risk factors, meta-analysis, systematic review",

author = "Paulina Orellana and Ariel Caviedes and Liset Gonzalez and Carolina Ochoa-Rosales and Danilo Carmona and Carolina Gonz{\'a}lez-Silva and Hern{\'a}n Hern{\'a}ndez and Britton, \{Gabrielle B.\} and Villarreal, \{Alcibiades E.\} and Victoria Campos and Hugh Hendrie and Juliana Acosta-Uribe and Pina-Escudero, \{Stefanie D.\} and Yokoyama, \{Jennifer S.\} and Natalia Vilor-Tejedor and Mario Parra and Hernando Santamaria-Garc{\'i}a and Agust{\'i}n Iba{\~n}ez and \{de la Cruz\}, Rolando and Claudia Duran-Aniotz",

note = "Publisher Copyright: {\textcopyright} 2026 The Author(s). Alzheimer's \& Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. {\textcopyright} 2026 The Author(s). Alzheimer's \& Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2026",

month = feb,

day = "1",

doi = "10.1002/alz.71224",

language = "English",

volume = "22",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

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Orellana, P, Caviedes, A, Gonzalez, L, Ochoa-Rosales, C, Carmona, D, González-Silva, C, Hernández, H, Britton, GB, Villarreal, AE, Campos, V, Hendrie, H, Acosta-Uribe, J, Pina-Escudero, SD, Yokoyama, JS, Vilor-Tejedor, N, Parra, M, Santamaria-García, H, Ibañez, A, de la Cruz, R & Duran-Aniotz, C 2026, 'Association of apolipoprotein E variants on Alzheimer's disease in Latin America: A systematic review and meta-analysis', Alzheimer's and Dementia, vol. 22, no. 2, e71224. https://doi.org/10.1002/alz.71224

TY - JOUR

T1 - Association of apolipoprotein E variants on Alzheimer's disease in Latin America

T2 - A systematic review and meta-analysis

AU - Orellana, Paulina

AU - Caviedes, Ariel

AU - Gonzalez, Liset

AU - Ochoa-Rosales, Carolina

AU - Carmona, Danilo

AU - González-Silva, Carolina

AU - Hernández, Hernán

AU - Britton, Gabrielle B.

AU - Villarreal, Alcibiades E.

AU - Campos, Victoria

AU - Hendrie, Hugh

AU - Acosta-Uribe, Juliana

AU - Pina-Escudero, Stefanie D.

AU - Yokoyama, Jennifer S.

AU - Vilor-Tejedor, Natalia

AU - Parra, Mario

AU - Santamaria-García, Hernando

AU - Ibañez, Agustín

AU - de la Cruz, Rolando

AU - Duran-Aniotz, Claudia

N1 - Publisher Copyright: © 2026 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. © 2026 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

PY - 2026/2/1

Y1 - 2026/2/1

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Caribbean

KW - Latin America

KW - genetic risk factors

KW - meta-analysis

KW - systematic review

UR - https://www.scopus.com/pages/publications/105030577856

UR - https://www.mendeley.com/catalogue/88d0d163-ba5d-3887-9b22-b01d494ba945/

U2 - 10.1002/alz.71224

DO - 10.1002/alz.71224

M3 - Article

C2 - 41724662

AN - SCOPUS:105030577856

SN - 1552-5260

VL - 22

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 2

M1 - e71224

ER -

Association of apolipoprotein E variants on Alzheimer's disease in Latin America: A systematic review and meta-analysis

Abstract

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