TOMM40 '523 Associations with Baseline and Longitudinal Cognition in APOE ɛ3 Homozygotes

J Alzheimers Dis. 2019;70(4):1059-1068. doi: 10.3233/JAD-190293.

Abstract

TOMM40 '523 is associated with Alzheimer's disease (AD), but APOE linkage disequilibrium confounds this association. In 170 APOE ɛ3 homozygotes, we evaluated relationships between short and very long TOMM40 alleles and longitudinal declines in three cognitive domains (attention, verbal memory, and executive function). We used factor analysis to create composite scores from 10 individual cognitive tests, and latent growth curve modeling adjusting for clinical status (normal, amnestic mild cognitive impairment, or AD) to summarize initial performance and change over three years. Relative to individuals with two very long TOMM40 alleles, APOEɛ3 homozygotes with one or two short alleles showed lower baseline cognitive performance regardless of clinical status. The number of short or very long TOMM40 alleles was not associated with longitudinal cognitive changes. In APOEɛ3 homozygotes from the University of Kansas Alzheimer's Disease Center cohort, an association between TOMM40 '523 and cognition is consistent with the possibility that TOMM40 influences cognition independent of APOE.

Keywords: APOE; TOMM40; cognition; factor analysis; longitudinal.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / genetics*
  • Apolipoprotein E3 / genetics*
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Genetic Association Studies / methods*
  • Genetic Variation / genetics
  • Homozygote*
  • Humans
  • Longitudinal Studies
  • Male
  • Membrane Transport Proteins / genetics*
  • Mental Status and Dementia Tests
  • Middle Aged
  • Mitochondrial Precursor Protein Import Complex Proteins

Substances

  • Apolipoprotein E3
  • Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • TOMM40 protein, human