The APOE*4 allele of the apolipoprotein E gene (APOE) is an important risk factor for Alzheimer's disease. It has been suggested that levels of apolipoprotein E (apoE) in plasma are increased in Alzheimer's disease. In this population-based study, we found that serum apoE levels were lower in Alzheimer patients compared to non-demented controls (0.75 micromol/l (SD 0.35), vs. 0.83 micromol/l (SD 0.40), P < 0.05). This finding is in accordance with lower serum apoE levels as observed in carriers of the APOE*4 allele, who are over-represented in Alzheimer's disease. After adjustment for age, sex, total protein, albumin level, body mass index and the APOE genotype, the difference in serum apoE levels largely disappeared. Our population-based study suggests that the differences in serum apoE level between Alzheimer patients and controls are mainly the result of differences in the distribution of the APOE genotype.