TOMM40-APOE haplotypes are associated with cognitive decline in non-demented Blacks

Alzheimers Dement. 2021 Aug;17(8):1287-1296. doi: 10.1002/alz.12295. Epub 2021 Feb 13.


Introduction: The goal was to investigate effects of APOE-TOMM40-'523 haplotypes on cognitive decline in non-demented non-Hispanic Blacks (NHB), and determine whether effects differ from non-Hispanic Whites (NHW).

Methods: The impact of zero to two copies of the '523-Short variant (S; poly-T alleles < 20) within apolipoprotein E (APOE) genotype on a composite measure of global cognition and five domains was examined.

Results: In NHB with ε3/ε3 (N = 294), '523-S/S was associated with faster decline in global cognition (β = -0.048, P = 0.017), episodic memory (β = -0.05, P = 0.031), and visuospatial ability (β = -0.037, P = 0.034) relative to those without '523-S. For NHB ε4+ (N = 182), '523-S/S had slower decline in global cognition (β = 0.047, P = 0.042) and visuospatial ability (β = 0.07, P = 0.0005) relative to '523-S non-carriers. NHB ε4+ with '523-S also had a slower rate of decline than NHWs ε4+ with '523-S.

Discussion: '523-S/S has a different effect on cognitive decline among NHB dependent on APOE allele. Differences in the effect of ε4-'523-S in NHB may explain prior mixed findings on ε4 and decline in this population.

Keywords: cognitive aging; cohort studies; genetics; memory.

MeSH terms

  • Aged
  • Alleles
  • Apolipoproteins E / genetics*
  • Black or African American* / genetics
  • Black or African American* / statistics & numerical data
  • Cognition / physiology
  • Cognitive Dysfunction / genetics*
  • Female
  • Genotype
  • Haplotypes / genetics*
  • Humans
  • Male
  • Membrane Transport Proteins / genetics*
  • Memory, Episodic
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Poly T


  • Apolipoproteins E
  • Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • TOMM40 protein, human
  • Poly T