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

## TL;DR

This study finds that the APOE ε4 allele strongly increases Alzheimer's risk in Latin America, with regional differences, while ε3 is protective and ε2 is not.

## Contribution

The largest regional meta-analysis of APOE variants and Alzheimer's in Latin America, revealing novel regional variability and ε2 allele findings.

## Key findings

- APOE ε4 allele increases Alzheimer's risk (OR 3.25) in Latin America.
- ε3 allele shows protective effect (OR 0.42), while ε2 does not.
- Regional variability in ε4/ε4 risk is highest in Ecuador (OR 13.29).

## 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.

This study is the largest regional apolipoprotein E meta‐analysis on Alzheimer's disease (AD) risk across Latin America.The ε4 allele is associated with AD risk, but with regional variability across Latin American and Caribbean (LAC) countries.The ε3 allele showed a protective effect in LAC populations (pooled odds ratio 0.42).The ε2 allele us not associated with protection in LAC, diverging from findings in other regions.Findings underscore the need for region‐specific dementia risk estimates.

This study is the largest regional apolipoprotein E meta‐analysis on Alzheimer's disease (AD) risk across Latin America.

The ε4 allele is associated with AD risk, but with regional variability across Latin American and Caribbean (LAC) countries.

The ε3 allele showed a protective effect in LAC populations (pooled odds ratio 0.42).

The ε2 allele us not associated with protection in LAC, diverging from findings in other regions.

Findings underscore the need for region‐specific dementia risk estimates.