Apolipoprotein E genotype and association between smoking and early onset Alzheimer's disease.

ObjectiveTo investigate the hypothesis that differential survival between smokers and non-smokers leading to a decrease in the frequency of the e4 allele of the apolipoprotein E gene may explain the inverse relation between smoking history and early onset Alzheimer's disease.DesignA population based case-control study.SettingThe four northern provinces of the Netherlands and metropolitan Rotterdam.Subjects175 patients with early onset Alzheimer's disease and two independent control groups of 159 and 457 subjects.Main outcome measuresFrequencies of the apolipoprotein e4 allele and relative risk of early onset Alzheimer's disease.ResultsThe inverse association between smoking history and early onset Alzheimer's disease could not be explained by a decrease in the frequency of the apolipoprotein e4 allele. Among carriers of this allele with a family history of dementia subjects with a history of smoking had a strongly reduced risk of early onset Alzheimer's disease (odds ratio 0.10 (95% confidence interval 0.01 to 0.87)).ConclusionsThe results suggest that the inverse relation between smoking history and early onset Alzheimer's disease cannot be explained by an increased mortality in carriers of the apolipoprotein e4 allele who smoke. The association is strongly modified by the presence of the apolipoprotein e4 allele as well as by a family history of dementia.