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

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Abstract
Objective: To investigate the hypothesis that differential survival between smokers and nonsmokers 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. Design: A population based case-control study. Setting: The four northern provinces of the Netherlands and metropolitan Rotterdam. Subjects: 175 patients with early onset Alzheimer's disease and two independent control groups of 159 and 457 subjects. Main outcome measures: Frequencies of the apolipoprotein e4 allele and relative risk of early onset Alzheimer's disease. Results: The 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)). Conclusions: The 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. Key messages This study shows that the inverse association between smoking history and early onset Alzheimer's disease cannot be explained by a shift in frequency of the apolipoprotein e4 allele The inverse relation was significant only in subjects with a family history of dementia who carry the e4 allele Our study suggests that clinical trials with nicotine or nicotine derivatives have the greatest chance of success in patients with familial Alzheimer's disease who carry the apolipoprotein e4 allele