BACKGROUND: The varepsilon4 allele of the apolipoprotein E (APOE) gene is a well-characterized genetic risk factor for Alzheimer disease (AD). The association between stroke and a higher risk for AD has also been reported. Our study sought to determine the relationship between the APOE gene and AD and the comorbid risk of stroke. METHODS: The subjects of this study consisted of 48 patients with AD and 48 members of a control group. All subjects were genotyped for APOE. RESULTS: The results clearly show a significant increased risk of AD in carriers of the APOE epsilon3/epsilon4 genotype (P = .003, odds ratio [OR] = 4.1) or epsilon4 allele (P = .001, OR = 4.2). The risk for stroke in AD patients was also increased for carriers of the APOE epsilon3/epsilon4 genotype (P = .02, OR = 9.0) and for carriers of the APOE epsilon4 allele (P = .004, OR = 5.5). CONCLUSIONS: The present study is the first to establish a relationship between APOE epsilon4 and concomitant AD and stroke in the Tunisian population.