Document Type
Article
Publication Date
5-9-2025
Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by cognitive decline and progressive functional impairment. 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 associated with an increased risk of AD, its impact varies across populations. This study investigated the prevalence of and association between APOE alleles and AD risk in a Ugandan cohort. This case-control study was conducted in Uganda, and included 87 participants (45 patients with AD and 42 healthy controls). Cognitive assessment was performed using the Montreal Cognitive Assessment (MoCA) and clinical diagnoses were based on the ICD-11 and DSM-5 criteria. Venous blood was collected for APOE genotyping by polymerase chain reaction. Statistical analyses, including logistic regression and generalized additive models (GAMs), were used to assess the association between APOE alleles and AD risk after adjusting for age, education, and sex. This study included 45 patients with AD and 42 healthy controls. The AD group was significantly older than controls (79.6 vs 73.0 years; P = .0006). The ϵ4 allele was common in both the AD (42.2%) and control groups (44.0%), which was higher than the 1000 Genomes African ancestry data. No significant association was found between the APOE genotype or allele dosage and AD risk after adjusting for age, sex, and education. However, the probability of AD increases with age, particularly among ϵ4 carriers with lower educational levels. While APOE ϵ4 status was associated with a higher predicted probability of AD in older adults, no statistically significant relationship was observed in the Ugandan cohort. These findings support the need for larger population-specific studies to explore APOE's role of APOE in AD risk across sub-Saharan Africa.
Keywords
Alzheimer's disease, APOE, case-control study, Uganda
Language
English
Publication Title
Medicine United States
Grant
D43NS118560
Rights
© 2025 the Author(s). This is an Open Access work distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Lwere, Kamada MMeda,b,c,*; Muwonge, Haruna PhDd; Sendagire, Hakim PhDa; Sajatovic, Martha PhDe; Gumukiriza-Onoria, Joy Louise MScf; Buwembo, Denis MPHg; Buwembo, William PhDh; Nassanga, Rita MMedi; Nakimbugwe, Rheem BScc; Nazziwa, Aisha MScc; Munabi, Ian Guyton PhDh; Nakasujja, Noeline PhDf; Kaddumukasa, Mark PhDj. Apolipoprotein E (APOE) and Alzheimer’s disease risk in a Ugandan population: A pilot case-control study. Medicine 104(19):p e42407, May 09, 2025. | DOI: 10.1097/MD.0000000000042407
Manuscript Version
Final Publisher Version