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The Association Between Apolipoprotein E Allele 4 and Late-Onset Alzheimer's Disease: Pathogenic Relationship or Differential Survival Bias

Jack E. Riggs, MD; Robert W. Keefover, MD
Departments of Neurology, Psychiatry, Medicine, and Community Medicine West Virginia University School of Medicine Morgantown, WV 26506-9180

Arch Neurol. 1994;51(8):750.

	Since this article does not have an abstract, we have provided the first 150 words of the full text PDF and any section headings.

Recent genetic epidemiological studies^1-3 have documented a significant association between the apolipoprotein E (ApoE) allele 4 (ApoE-4) and late-onset familial and sporadic Alzheimer's disease (AD). This association is so impressive that one group of investigators concluded that "homozygosity for ApoE-4 was virtually sufficient to cause AD by age 80."¹ However, the bane of any epidemiological association is bias.⁴ We suggest that selection bias may have significantly contributed to, or even produced, the observed association between ApoE-4 and late-onset AD.

The three common ApoE alleles are 2, 3, and 4. The relative frequencies of these alleles in healthy population samples are about 8%, 76%, and 14%, respectively.^5-6 Individuals with ApoE-4 have an increased risk of premature coronary artery disease.^7-9 As a result of earlier mortality due to heart disease, the relative frequency of the 4 allele was predicted, and found, to decline with age.^10-11 This . . . [Full Text PDF of this Article]

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