From Cohort to Molecular Insights: Integrating an African-Centric iPSC Biobank to Decipher the Role of APOE and Ancestry in Alzheimer's Disease (360G-Wellcome-310522_Z_24_Z)

Despite the notable influence of genetic background on health, biomedical research is critically hindered by the lack of models to study the influence of African genetic diversity on health outcomes. This gap is especially pertinent in our understanding of Alzheimer's disease (AD), where risk variants like APOE ε4 and key hallmarks—Aβ and tau—show ancestry-dependent effects. Here, I propose to decipher how ancestry and APOE influence AD pathogenesis using cells from African and European backgrounds. We hypothesize that the interaction between APOE variants and ancestral backgrounds uniquely modulates cellular gene expression, function, and responses to AD pathology. Building on my previous work, networks across continents, and patient pool from collaborating Nigerian hospitals, we will address this by 1) Establishing the first deeply phenotyped AD cohort in Northern Nigeria, 2) Building and distributing stem cell models to the scientific community from the cohort by developing Africa’s first open-access stem cells biobank, 3) Delineating the distinct effects of ancestral background and APOE variants on AD phenotypes in stem cells models. This will significantly advance the understanding of AD across populations and contribute to global breakthroughs by facilitating disease modelling and drug screening in African genetic backgrounds using our pioneering iPSC resource.