A polymorphism in the regulatory region of APOE associated with risk for Alzheimer's dementia

Nat Genet. 1998 Jan;18(1):69-71. doi: 10.1038/ng0198-69.


The epsilon4 allele of the apolipoprotein E gene (APOE) has been associated with an increased risk of developing Alzheimer's disease (AD; refs 1,2). However, it is apparent that the APOEepsilon4 allele alone is neither necessary nor sufficient to cause the disease. We have recently found three new polymorphisms within the APOE transcriptional regulatory region (M.J.A. et al., manuscript submitted) and now establish an association between one of these polymorphisms (-491A/T) and dementia as observed in Alzheimer's disease, in two independent clinical populations. The results suggest that homozygosity of a common variant (-491A) is associated with increased risk for AD, and that this association is independent of APOEepsilon4 status. In vitro studies suggest that the -491A/T polymorphism may increase risk for AD by altering the level of ApoE protein expression.

Publication types

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

MeSH terms

  • Alleles
  • Alzheimer Disease / genetics*
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Dementia / genetics
  • Gene Frequency
  • Humans
  • Polymorphism, Genetic*
  • Regulatory Sequences, Nucleic Acid*
  • Risk Factors
  • Tumor Cells, Cultured


  • Apolipoprotein E4
  • Apolipoproteins E

Associated data

  • GENBANK/AF055343