GENETIC ASSOCIATION STUDIES BETWEEN DEMENTIA OF THE ALZHEIMERS TYPE AND 3 RECEPTORS FOR APOLIPOPROTEIN-E IN A CAUCASIAN POPULATION

The epsilon 4 allele of the apolipoprotein E gene (ApoE) is associated with an increased risk for sporadic and some familial forms of Alzhei mer's disease (AD) but the precise mechanism of pathogenesis is unknow n. ApoE is a ligand for at least three receptors in the central nervou s system, low density lipoprotein receptor (LDL-R), very low density l ipoprotein receptor VLDL-R and low density lipoprotein-like receptor ( LRP). We have tested for association between these receptors and demen tia of the Alzheimer's type (DAT) in a clinically based sample of Cauc asian cases and age-matched controls. In contrast to findings in a Jap anese cohort we detected no association between DAT and a polymorphism in the VLDL-R gene. No association was detected with the LDL-R gene. We observed a possible association between the 87 allele of a polymorp hism within the LRP gene and DAT which remained significant after corr ection for multiple testing. When the effects of known risk factors fo r AD such as ApoE epsilon 4 were applied, the effect of LRP no longer reached conventional levels of statistical significance. Nevertheless, LRP is a plausible candidate gene and we may be observing a minor ris k factor that will require further examination in other large independ ent samples to assess whether it truly modifies susceptibility to DAT. (C) 1997 Elsevier Science Ireland Ltd.