Testing for Interactions Between APOE and Klotho Genotypes on Cognitive, Dementia, and Brain Imaging Metrics in UK Biobank

J Alzheimers Dis. 2021;83(1):51-55. doi: 10.3233/JAD-210181.

Abstract

Recent research suggests genetic variation in the Klotho locus may modify the association between APOE ɛ4 and cognitive impairment. We tested for associations and interactions between these genotypes versus risk of dementia, cognitive abilities, and brain structure in older UK Biobank participants. Klotho status was indexed with rs9536314 heterozygosity (versus not), in unrelated people with versus without APOE ɛ4 genotype, corrected for various confounders. APOE ɛ4 associated with increased risk of dementia, worse cognitive abilities, and brain structure. Klotho was associated with better reasoning. There were no interactions; potentially suggesting an age- and pathology-dependent Klotho effect.

Keywords: APOE; Klotho; brain; cognitive; dementia.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoprotein E4 / genetics*
  • Biological Specimen Banks*
  • Brain
  • Cognitive Dysfunction* / epidemiology
  • Cognitive Dysfunction* / genetics
  • Dementia* / epidemiology
  • Dementia* / genetics
  • Female
  • Genotype
  • Glucuronidase / genetics*
  • Heterozygote
  • Humans
  • Klotho Proteins
  • Male
  • Middle Aged
  • Mutation / genetics
  • Neuroimaging*
  • Prospective Studies
  • United Kingdom / epidemiology

Substances

  • Apolipoprotein E4
  • Glucuronidase
  • Klotho Proteins