Browse by author
Lookup NU author(s): Professor Raj KalariaORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025 The Alzheimer's Association. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association. BACKGROUND: The "Recruitment and Retention for Alzheimer's Disease Diversity Genetic Cohorts in the Alzheimer's Disease Sequencing Project" (READD-ADSP) is building a resource aimed at increasing genetic ancestry representation in Alzheimer's disease (AD) studies to advance our ability to leverage all genetic variation in solving AD for everyone. READD-ADSP includes four US sites and ten countries in sub-Saharan Africa part of the Africa Dementia Consortium (AfDC). The main goal is to characterize AD genetic risk and protective factors to understand AD mechanisms that can inform prevention and treatment globally. In this resource, we explored known AD loci using genetic data from West and East Africa: Nigeria, Ghana, Kenya, Ethiopia and Mozambique. METHOD: We performed genome-wide association analysis on 275 AD cases and 278 cognitively unimpaired controls. We estimated population substructure using PC-AiR, which is robust to known and cryptic relatedness. We investigated known AD loci from non-Hispanic White (NHW) and African American (AA) genome-wide association studies (Bellenguez et al. and Ray et al.). For association analysis, we employed a mixed-model regression approach (SAIGE) where we controlled for age, gender, population substructure, and relatedness. To further explore genetic diversity, we calculated global ancestry using ADMIXTURE. RESULT: Admixture and principal component analysis revealed distinct ancestral patterns between West and East Africa, as well as substantial differential distributions of variation within each region. Among the previously reported lead genetic markers in NHW and AA GWAS studies, only APOE e4 (OR=2.0; CI:1.4-3.0; p = 3.1x10-8) reached genome-wide significance. Three additional loci (ABCA7, BCKDK/KAT8, TREML2) showed nominal significance for AD risk. CONCLUSION: Our findings confirm the role of APOE e4 in AD risk among African ancestries and its smaller effect size relative to NHW populations, and replicate three additional loci (ABCA7, BCKDK/KAT8, TREML2) that show nominal associations with AD. Admixture and principal component analysis underscores the extensive genetic variability among the African diaspora. Ongoing data collection through the AfDC and READD-ADSP at large to reach 13,000 total participants across global populations will continue to enhance understanding of AD pathogenesis. By leveraging genetic diversity from multiple populations, we can ultimately accelerate the discovery of interventions that benefit all communities.
Author(s): Scott KM, Rajabli F, Akinyemi JO, Adams LD, Coker M, Akinwande K, Diala S, Whitehead PG, Ogunronbi M, Hamilton-Nelson KL, Damasceno A, Zaman AF, Zewde YZ, Ayele BA, Caban-Holt AM, Ndetei D, Griswold AJ, Sarfo FS, Blanton SH, Akpalu A, Cuccaro ML, Wahab K, McInerney KF, Obiako R, Baiyewu O, Mena PR, Okubadejo NU, Owolabi MO, Chavez J, Martinez IM, Kunkle BW, Vance JM, Reitz C, Tosto G, Williams SM, Bush WS, Kalaria R, Haines JL, Ogunniyi A, Byrd GS, Akinyemi RO, Pericak-Vance M
Publication type: Article
Publication status: Published
Journal: Alzheimer's & Dementia
Year: 2025
Volume: 21
Issue: S1
Online publication date: 24/12/2025
Acceptance date: 02/04/2018
Date deposited: 06/01/2026
ISSN (print): 1552-5260
ISSN (electronic): 1552-5279
Publisher: John Wiley and Sons Inc.
URL: https://doi.org/10.1002/alz70855_106725
DOI: 10.1002/alz70855_106725
PubMed id: 41444752
Notes: Supplement: Basic Science and Pathogenesis
Altmetrics provided by Altmetric
