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Basic Science and Pathogenesis.

Ryan Dacey1,2, Xudong Han1,2, Shruti Durape2,3,4

  • 1Department of Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.

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This study found that the CR1 gene is more strongly associated with Alzheimer's disease (AD) risk in individuals with lower educational attainment. This suggests immune mechanisms may mediate the link between education and AD.

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Area of Science:

  • Genetics
  • Neuroscience
  • Epidemiology

Background:

  • Alzheimer's disease (AD) risk is influenced by genetic and environmental factors.
  • Higher educational attainment is linked to lower AD risk, but the underlying mechanisms are unclear.
  • Investigating gene-environment interactions may explain AD heritability.

Purpose of the Study:

  • To explore genetic associations with AD risk through gene-environment interactions.
  • To examine the relationship between single nucleotide polymorphisms (SNPs) and educational attainment in AD.
  • To conduct education-stratified analyses to understand differing genetic risks.

Main Methods:

  • Genome-wide association studies (GWAS) were performed on over 27,000 participants (NHW and AFA).
  • Analyses included SNP-by-education interaction terms and stratification by median education level.
  • Top GWAS hits were assessed for association with cognitive trajectories (memory, language, executive function).

Main Results:

  • A genome-wide significant association was found for the CR1 gene (rs12037841) in individuals with lower educational attainment (p=3.1x10^-10).
  • This association was present in both non-Hispanic white and African American participants.
  • The SNP rs12037841 was linked to faster cognitive decline in memory and language among those with lower education.

Conclusions:

  • The CR1 gene, involved in the complement pathway, shows a stronger association with AD risk in individuals with lower educational attainment.
  • This suggests that immune-related mechanisms may moderate the protective effect of education against AD.
  • Findings highlight the role of gene-environment interactions in AD pathogenesis.