Association of the C766T polymorphism of the low-density lipoprotein receptor-related protein gene with Alzheimer's disease.

The low-density lipoprotein receptor-related protein (LRP) is one of the most important cholesterol receptors in the brain. Gene variation of its ligand, apolipoprotein E, is a major genetic risk-factor for Alzheimer's disease (AD). The C-allele of the silent C766T polymorphism in exon 3 of the LRP gene might be associated with AD, however, results are conflicting and thus discussed controversially. Consequently, we compared the prevalence of this polymorphism in a homogenous cohort of patients with AD and control subjects. We found that carriers of a C-allele were at lower risk of AD; in agreement with this observation, AD patients who were carriers of a C-allele presented with a later age at onset of the disease than carriers of the TT genotype. These data suggest that LRP polymorphism influences the risk as well as the age at onset of AD. Our results contrast with other studies which described the C-allele to be a risk-factor for AD, but are in line with a recent publication on the effect of LRP polymorphism on longevity and on the risk for coronary artery disease. Further research on LRP polymorphisms is needed to evaluate their effects on the risk of AD, on coronary artery disease and on longevity. Copyright 2003 Wiley-Liss, Inc.