The -491AA polymorphism in the APOE gene is associated with increased plasma apoE levels in Alzheimer's disease

RECENT evidence suggests that a polymorphism in the regulatory region of the apolipoprotein E gene (APOE) is associated with an increased risk for developing Alzheimer's disease (AD) independent of that conveyed by the epsilon 4 allele of APOE. Previous work by our group indicated that plasma apolipoprotein E (apoE) levels were elevated in AD, raising the possibility that the genotype might modify AD risk by increasing expression of the APOE gene. In a total of 638 individuals the -491AA genotype was significantly associated with AD (P < 0.005) while the TT genotype was associated with controls (P < 0.005). In 138 individuals the AA genotype showed significantly higher plasma apoE levels, independent of epsilon 4 and AD status (P<0.01) as well as within control and AD groups (P<0.05). Within the AD group the AA genotype showed increased apoE levels when compared to AA controls (P<0.0001). These results suggest that the -491 AA genotype is associated with increased plasma apoE levels, providing a potential basis for elucidating how that genotype increases the risk for developing AD. NeuroReport 10:879-882 (C) 1999 Lippincott Williams & Wilkins.