As part of the ApoEurope Project, apolipoprotein E (apo E) common polymorphism and serum concentration were determined in 489 Alzheimer's disease patients and 429 controls. Patients and controls were recruited through nine centres in eight European countries. Age, sex ratios and education levels of both case and control populations were similar, although discrete differences appeared between centres. The prevalence of the epsilon4 allele was higher in Alzheimer's disease than in controls (increased by 140%), while serum apo E concentration was lower by 11.2% (p<0.001). In addition, serum total cholesterol and triglyceride concentrations were lower in Alzheimer's disease (p<0.001), while that of apo Al was not affected. The decrease in serum apo E concentration was not accounted for by the epsilon4 allele, age or gender, suggesting that apo E concentration might represent an additional risk factor for Alzheimer's disease, complementary and independent of the epsilon4 allele. Further analysis will be aimed at determining whether the quantitative link between apo E concentration and Alzheimer's disease occurs through the effect of apo E genotype on lipid parameters or by other mechanisms.