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From the Departments of Clinical Biochemistry (Drs. Frikke-Schmidt and Tybjærg-Hansen) and Vascular Surgery (Dr. Moes Grønholdt), Rigshospitalet, Copenhagen University Hospital; Department of Clinical Biochemistry (Dr. Nordestgaard), Herlev University Hospital; and Copenhagen City Heart Study (Drs. Nordestgaard, Thudium, and Tybjærg-Hansen), Bispebjerg University Hospital, Copenhagen, Denmark.
Received March 20, 2000. Accepted in final form October 10, 2000.Address correspondence and reprint requests to Dr. A. Tybjærg-Hansen, Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark; e-mail: at-h{at}rh.dk
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 
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 
43 and 44 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 43 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 43 and 44 genotypes was 37 and 20% in the general population, whereas the fraction of OD that could be attributed to the 43 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.
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