Genetic association studies between Alzheimer's disease and two polymorphisms in the low density lipoprotein receptor-related protein gene

Neurosci Lett. 1998 Mar 13;244(2):65-8. doi: 10.1016/s0304-3940(98)00141-4.


The E*4 allele of apolipoprotein E (APOE) is a major risk factor for Alzheimer's disease (AD) but the underlying mechanism is unknown. The low density lipoprotein receptor-related protein (LRP) is directly involved in APOE metabolism and therefore may alter the risk of AD associated with APOE. Two common polymorphisms, a tetranucleotide repeat in the 5'-region and a same-sense mutation in exon 3, are present in the LRP gene. Three studies have reported conflicting association of the tetranucleotide polymorphism with AD. The only study of the exon 3 polymorphism found a significant association with AD. In this study we examined the association of these two LRP polymorphisms with sporadic late-onset AD. No significant association was observed between the tetranucleotide polymorphism and AD. While the overall genotype and allele frequencies for the LRP exon 3 polymorphism were comparable between AD cases and controls, the frequency of the TT genotype was significantly higher in controls than AD (5.7% vs. 2.5%; P < 0.01). Stratification of the data by APOE genotypes indicated that the protective effect associated with the TT genotype was confined to APOE*4 carriers. Although the effect of the exon 3 polymorphism in our sample is small compared to the previous study, this warrants additional studies to confirm this putative association.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age of Onset
  • Aged
  • Alzheimer Disease / genetics*
  • Apolipoprotein E4
  • Apolipoproteins E / genetics
  • Exons
  • Female
  • Genotype
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Male
  • Microsatellite Repeats*
  • Point Mutation
  • Polymorphism, Genetic*
  • Receptors, Immunologic / genetics*
  • Receptors, LDL / genetics
  • Reference Values


  • Apolipoprotein E4
  • Apolipoproteins E
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Receptors, Immunologic
  • Receptors, LDL