The relationship between risk of late-onset Alzheimer’s disease and TOMM40-523' repeat size

Takeaway

  • Poly-T TOMM40-523' variant size does not explain the large difference in risk of late-onset Alzheimer’s disease (LOAD) between patients with African or European local genomic ancestry (LGA) on the APOE ε4 haplotype.

  • Increasing TOMM40-523' repeat size is associated with decreased risk of LOAD in carriers of the homozygous APOE ε3 haplotype with European LGA.

Why this matters

  • The APOE ε4 allele in African and African Americans confers a lower risk of LOAD compared with Europeans, which may be attributable to LGA within the APOE haplotype. TOMM40-523' repeat size varies in length by individual and race, possibly influencing the transcription of APOE and affecting the risk of developing LOAD.

  • Previous studies have analyzed the relationship between TOMM40-523' length and LOAD framed in the context of global genetic ancestry, though this is the first to adjust for LGA and thus offer the most accurate insight into this relationship.