APOE promoter polymorphisms and dementia in the elderly.

Previous observations suggest a contribution of two APOE promoter polymorphisms (-219 G/T and -491 A/T) in dementia. From two independent populations of elderly (mean age of 84 and 85 years old, respectively), we observed that subjects bearing the -219T allele were at increased risk of dementia (OR = 1.9 (95% CI, 1.3-2.8), P = 0.0003) or AD (OR = 2.0 (95% CI, 1.2-3.4), P < 0.008). Conversely, the -491 A/T variant was not associated with this risk of dementia in the elderly, as previously described. Haplotype estimations including the two promoter and the coding APOE polymorphisms indicated that the -491A/-219T/4 haplotype was at risk for the development of dementia (OR = 3.5 (95% CI, 2.5-5.0), P < 0.0001), whereas the -491A/-219G/4 haplotype was not (OR = 1.1 (95% CI, 0.6-2.1)). Similar results were observed when restricted to Alzheimer's disease. In conclusion, these data indicate that the -219 G/T polymorphism is a genetic determinant of dementia in the elderly, independently of the 4 allele.