Background: The APOE polymorphism is an important modulator of plasma lipoproteins and a risk factor for AD. The hypothesis that APOE genotype, through its effect on lipoproteins, is a common risk factor for ischemic cerebrovascular disease (ICVD), AD, and other dementia (OD) was tested.
Methods: The authors genotyped 9241 individuals from the general population, 452 patients with ICVD and > or = 50% stenosis of the carotid arteries, and 75 patients with ICVD before the age of 50 years. Among the individuals from the general population, 211 had ICVD, 26 had AD, and 28 had OD.
Results: The APOE polymorphism was not associated with ICVD in any of the three patient groups. In contrast, the epsilon43 and epsilon44 genotypes were associated with 3- and 10-fold risks of AD (95% CI = 1.4 to 8.0 and 2.5 to 41.0), and the epsilon43 genotype was also associated with a 2.5-fold risk of OD (95% CI = 1.1 to 5.5). These increases in risk were not abolished by adjustment for lipids and lipoproteins. The fraction of AD that could be attributed to the epsilon43 and epsilon44 genotypes was 37 and 20% in the general population, whereas the fraction of OD that could be attributed to the epsilon43 genotype was 26%.
Conclusion: The APOE polymorphism is a risk factor for AD and OD independent of lipid and lipoprotein levels but does not affect the risk of ICVD.