FIVE YEARS ago, Saunders et al1 reported the strong and surprising association between apolipoprotein E (apoE) genotypes and sporadic Alzheimer disease (AD). There are 3 common alleles of the apoE gene: ϵ2, ϵ3, and ϵ4, with allele frequencies in the general population of approximately 0.08, 0.78, and 0.14, respectively. There is universal agreement that the ϵ4 allele is a powerful risk factor for AD that lowers the age of dementia onset, whereas the ϵ2 allele may protect against AD or at least delay its onset. During the past 5 years, research on apoE and AD has centered on 3 broad questions: (1) Do apoE genotypes influence the phenotype of AD? (2) Can the apoE genotype be used to diagnose AD? (3) What are the biological mechanisms whereby the ϵ4 allele increases the risk of developing AD? The study by Jonker et al2 touches on each of these questions. The strengths of this study include a large epidemiologically defined population that was tested annually with standardized cognitive measures for 3 years. This careful attention to protocol design buttresses their conclusions.
Growdon JH. Apolipoprotein E and Alzheimer Disease. Arch Neurol. 1998;55(8):1053-1054. doi:10.1001/archneur.55.8.1053