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Basic Science and Pathogenesis.

Kyle M Scott1, Farid Rajabli2,3, Joshua O Akinyemi4

  • 1University of Miami Miller School of Medicine, Miami, FL, USA.

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|December 24, 2025
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Summary
This summary is machine-generated.

This study highlights the importance of genetic diversity in Alzheimer's disease (AD) research. APOE e4 is confirmed as an AD risk factor in African ancestries, with other loci showing potential associations.

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Area of Science:

  • Genetics
  • Neuroscience
  • Population Health

Background:

  • Alzheimer's disease (AD) research lacks diverse genetic representation.
  • The Recruitment and Retention for Alzheimer's Disease Diversity Genetic Cohorts in the Alzheimer's Disease Sequencing Project (READD-ADSP) aims to increase diversity.
  • This study focuses on genetic data from West and East Africa.

Purpose of the Study:

  • To characterize AD genetic risk and protective factors in diverse African populations.
  • To understand AD mechanisms for global prevention and treatment.
  • To explore known AD loci in African genetic data.

Main Methods:

  • Genome-wide association analysis on AD cases and controls.
  • Estimation of population substructure using PC-AiR.
  • Investigation of known AD loci from previous GWAS studies.
  • Mixed-model regression analysis (SAIGE) and global ancestry calculation (ADMIXTURE).

Main Results:

  • Distinct ancestral patterns were observed between West and East Africa.
  • APOE e4 reached genome-wide significance for AD risk (OR=2.0).
  • Three additional loci (ABCA7, BCKDK/KAT8, TREML2) showed nominal significance for AD risk.

Conclusions:

  • Confirms APOE e4's role in AD risk across African ancestries, with a smaller effect size than in non-Hispanic White populations.
  • Replicates ABCA7, BCKDK/KAT8, and TREML2 loci with nominal associations to AD.
  • Emphasizes the extensive genetic variability within the African diaspora and the need for diverse data to advance AD understanding and interventions.