Apo E and Apo CI loci are associated with dementia in younger but not older late-onset cases.

Numerous groups have confirmed that apolipoprotein E allelic variation accounts for a proportion of the genetic risk for late-onset Alzheimer's disease (AD). However, there is a paucity of data on the impact of this locus on the overall risk of dementia (as opposed to AD) in the elderly. Most studies have ascertained specifically AD cases from hospital clinics or brain banks and many demented cases have vascular dementia or mixed AD and vascular pathology. We have examined the closely linked apo E and apo CI loci in demented cases and non-demented controls from two community-based aged Cambridgeshire populations: the rural Ely population (cohort 1) comprised 60 pairs of demented and non-demented elderly individuals, with a mean age of 84.2 years (SD = 6.11); the Cambridge city population (cohort 2) comprised 81 pairs all aged over 84 with a mean age of 87.7 years (SD = 2.9). The younger Ely cohort showed significant allelic associations with dementia at the apo E and apo CI loci, which were not replicated in the older Cambridge cohort. These data suggest the possibility of age-dependent penetrance for different candidate genes in late-onset dementia. We propose a number of explanations to account for the stronger associations we observed between dementia and apo CI, compared to the neighbouring apo E locus. Our data are compatible with the possibility that specific alleles or genotypes may confer different risks for overall dementia, compared to AD.