Landscape of Apolipoprotein (APOE) in the Emirati Population and Recommendations for a Genotyping Approach for Amyloid-Beta Monoclonal Antibodies (Aβ-mAbs) in Alzheimer's Disease Patients.

BACKGROUND

Apolipoprotein E (APOE) genotyping is increasingly recognized as a biomarker to support treatment decisions for Alzheimer's disease (AD) with the introduction of anti-amyloid monoclonal antibodies as promising therapeutic options. Although not yet incorporated into formal pharmacogenomic guidelines, regulatory authorities acknowledge its potential role in advancing precision medicine approaches.

METHODS

We reviewed AD cases diagnosed in 2024 from the Department of Health - Abu Dhabi records and assessed monoclonal antibody prescribing patterns. APOE genotypes were determined using the two defining variants, APOE rs429358 and rs7412, using whole-genome sequencing data from 506,734 participants enrolled in the Emirati Genome Program.

RESULTS

In 2024, 1,285 individuals were diagnosed with AD. Aducanumab was prescribed to eight patients between 2022 and 2024. In the Emirati Genome Program cohort, the allele frequencies of rs429358 and rs7412 were 8.3% and 4.2%, respectively. The most prevalent APOE genotype was ε3/ε3 (77.9%). The APOE ε4 risk allele was observed in 14.7% of participants, including 0.9% who were homozygous for ε4, while the protective APOE ε2 allele was present in 7.5%.

CONCLUSION

APOE profiling supports genotype-informed treatment strategies for anti-amyloid therapies. These findings establish a population-specific framework for integrating genetic information into the Emirati Genome Program pharmacogenomic report, enhancing precision medicine approaches for AD management in the UAE.