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

ABSTRACT

The epsilon 4 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 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 risk factor that will require further examination in other large independent samples to assess whether it truly modifies susceptibility to DAT.