Frank Balikoowa

Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a progressive decline in cognitive and functional abilities. The Apolipoprotein E (APOE) gene, particularly its ε2, ε3, and ε4 alleles, plays a crucial role in lipid metabolism and has been implicated in AD pathogenesis. Although the APOE ε4 status is strongly associated with an increased risk of AD globally, its impact varies across diverse ethnocultural populations. This study aimed to evaluate the prevalence of and association between APOE alleles and AD risk within a population in southwestern Uganda.

Methods: A case-control study was conducted in the southwestern region of Uganda, comprising 98 participants (54 patients diagnosed with AD and 44 age-matched controls). Cognitive assessment was systematically performed using the Montreal Cognitive Assessment (MoCA). Clinical diagnoses were established based on the criteria specified in the ICD-11 and DSM-5. Venous blood samples were collected from all participants for APOE genotyping via polymerase chain reaction (PCR). Statistical analyses, incorporating logistic regression and generalized additive models (GAMs), were utilized to assess the specific association between APOE alleles and AD risk after adjusting for age, education, and sex.

Results: The final study cohort included 54 patients with AD and 44 controls. The AD group was significantly older than the control group (89.6 vs. 73.0 years; P = .0005). The APOE ε4 allele was highly prevalent in both the AD (52.2%) and control (46.0%) groups, a rate notably higher than reference data from the 1000 Genomes African ancestry datasets. No statistically significant direct association was found between overall APOE genotype or allele dosage and AD risk after controlling for age, sex, and education. However, the probability of developing AD increased substantially with age, particularly among ε4 carriers with lower educational attainment levels.