DOI: 10.1177/13872877261475340 ISSN: 1387-2877

APOE ε4 and late-onset Alzheimer's disease in Syria: A case-control study

Ibrahim Labbad, Lama A. Youssef, Maha Rustom, Mohamad Shehadeh Agha

Background

The apolipoprotein E ( APOE ) ε4 allele is the strongest known genetic risk factor for late-onset Alzheimer's disease (AD), but its prevalence and impact vary substantially across populations. No previous study has characterized APOE allele distribution among Syrian patients with AD.

Objective

This investigation aimed to assess the association between APOE genotypes and AD risk in a Syrian cohort.

Methods

In this case–control study, genomic DNA was extracted from 52 clinically diagnosed AD patients and 38 cognitively healthy controls. The APOE genotype was determined by direct sequencing of the rs429358 and rs7412 polymorphisms defining the ε2, ε3, and ε4 alleles. Genotypic and allelic frequencies were compared using Fisher's exact test, and Hardy–Weinberg equilibrium was assessed in the controls.

Results

The ε3/ε3 genotype was predominant in both groups (73.1% of cases, 94.7% of controls). The ε3/ε4 genotype appeared in 23.1% of AD patients but was absent among controls (Corrected OR = 12.37, 95% CI = 0.65–233.7, p < 0.01). The overall ε4 allele frequency in patients (0.117) was significantly higher than in controls (0.000) (Corrected OR = 10.76, 95% CI = 0.59–195.7, p < 0.01). The ε2/2, ε4/4, and ε2/4 genotypes were not detected in any participants.

Conclusions

This study is the first to investigate the prevalence of the APOE ε4 allele in Syrian patients with Alzheimer's disease. These results underscore the importance of investigating genetic architectures when assessing AD risk and call for larger, multi-center studies across the Middle East to elucidate the interplay between APOE variants and metabolic determinants of cognitive decline.

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