Genetic association studies between dementia of the Alzheimer's type and three receptors for apolipoprotein E in a Caucasian population

The ε4 allele of the apolipoprotein E gene (ApoE) is associated with an increased risk for sporadic and some familial forms of Alzheimer's disease (AD) but the precise mechanism of pathogenesis is unknown. ApoE is a ligand for at least three receptors in the central nervous system, low density lipoprotein receptor (LDL-R), very low density lipoprotein receptor VLDL-R and low density lipoprotein-like receptor (LRP). We have tested for association between these receptors and dementia of the Alzheimer's type (DAT) in a clinically based sample of Caucasian cases and age-matched controls. In contrast to findings in a Japanese 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 polymorphism within the LRP gene and DAT which remained significant after correction for multiple testing. When the effects of known risk factors for AD such as ApoE ε4 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 risk factor that will require further examination in other large independent samples to assess whether it truly modifies susceptibility to DAT.