Polymorphisms of the apolipoprotein E gene regulatory region and of the LDL receptor gene in late-onset Alzheimer's disease in relation to the plasmalipidic pattern

Two new polymorphisms in the regulatory region of the apolipoprotein E gene , -491 A/T and -427 T/C, have been reported to be associated with the risk of Alzheimer's disease (AD). Moreover, in vitro studies suggest that the tw o polymorphisms modulate the levels of apoE protein expression. We examined these two polymorphisms, as well as the Mspl polymorphism in the LDL recep tor gene, in a series of elderly patients with late-onset sporadic AD and i n an age-matched control group but failed to find any kind of association b etween these genetic features and an increased risk of AD. In the same samp les we investigated the relationships between various genotypes and plasma lipid levels. Since the well-known effect of the three-allelic APOE polymor phism on plasma lipid levels could mask the effect of other polymorphisms, the analyses were performed taking into account the APOE genotype. The two regulatory region polymorphisms had significant effects only on the apoE le vels. The -427 TT homozygotes had lower, and the -491 AA homozygotes had hi gher levels of apoE than other genotypes. This result confirmed in vivo the already observed in vitro effects of -491 P/T and -427 T/C polymorphisms o n APOE promoter transcription activity. Copyright (C) 2001 S. Karger AG, Ba sel.