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Apolipoprotein E: risk factor for Alzheimer disease

M S Tsai1, E G Tangalos, R C Petersen

  • 1Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905.

American Journal of Human Genetics
|April 1, 1994
PubMed
Summary

The apolipoprotein E (APOE) epsilon 4 allele is significantly more frequent in Alzheimer disease (AD) patients than controls. This APOE variant is a key risk factor for developing AD and is associated with an earlier age of onset.

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Area of Science:

  • Genetics
  • Neuroscience
  • Epidemiology

Background:

  • The apolipoprotein E (APOE) gene exists in three common alleles: epsilon 2, epsilon 3, and epsilon 4.
  • These alleles form six genotypes influencing disease susceptibility.

Purpose of the Study:

  • To investigate the association between the APOE-epsilon 4 allele and late-onset Alzheimer disease (AD).
  • To determine if APOE-epsilon 4 is a risk factor for AD susceptibility.

Main Methods:

  • A case-control study involving 77 patients with late-onset AD and 77 age- and sex-matched controls.
  • Genotyping for APOE alleles and statistical analysis of allele and genotype frequencies.

Main Results:

  • The APOE-epsilon 4 allele frequency was significantly higher in AD patients (0.351) compared to controls (0.130).

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  • Genotype frequencies differed, with APOE-epsilon 4/epsilon 3 common in AD and APOE-epsilon 3/epsilon 3 in controls.
  • Homozygosity for APOE-epsilon 4 was found in 9 AD patients but none in controls.
  • The odds ratio for AD was 4.6 for one or two epsilon 4 alleles and 3.6 for heterozygosity.
  • Increased APOE-epsilon 4 alleles correlated with an earlier median age of AD onset (74 years for two alleles vs. 83 years for none).

    • Conclusions:

    • The APOE-epsilon 4 allele is strongly associated with late-onset Alzheimer disease.
    • APOE-epsilon 4 is a significant risk factor for AD susceptibility in the general population.
    • The presence of APOE-epsilon 4 alleles influences the age of onset for Alzheimer disease.