The low density lipoprotein receptor-related protein (LRP) gene is a candidate gene for Alzheimer's disease (AD) due to its role as a receptor for apolipoprotein E (apoE), a major genetic risk factor for late-onset familial and sporadic AD. Recently, several studies have reported a correlation between a polymorphism (C766T) in exon 3 of LRP and AD. We examined this polymorphism in a Caucasian population of 225 neuropathologically confirmed cases with AD and 187 elderly cases without any AD neuropathological changes. We found that the exon 3 LRP C/C genotype was slightly but not significantly higher in the AD group when compared to the control group. A meta-analysis of previous studies revealed only a weak correlation of this polymorphism with AD (odds ratio 1.34, [95% CI 1.16-1.54], P < 0.0001). These data indicate that the polymorphism in exon 3 of LRP is only a minor risk factor for AD and that another locus on chromosome 12 is likely responsible for the associations observed in other studies. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.