Elsevier

Neuroscience Letters

Volume 244, Issue 2, 13 March 1998, Pages 65-68
Neuroscience Letters

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

https://doi.org/10.1016/S0304-3940(98)00141-4Get rights and content

Abstract

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.

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Acknowledgements

This work was supported by NIH grants AG 13672 and AG05133. The technical and clerical help of Mr. Michael Carlin and Ms. Jeanette Norbut, respectively are greatly appreciated.

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    For LRP1 C766T, in the APOE ε4 positive subgroups, the frequency of the T allele (p = 0.004) and the T/T genotype (p = 0.027) was lower in the patients with SAD than in the control subjects and the LRP1 C766T T allele may decrease the risk for development of SAD in APOE ε4 carriers in the Chinese Northern Han population. This result is similar to that reported by Kamboh et al.18 and Hatanaka et al.19 Some investigations have shown that the LRP1 C766T polymorphism is related to the severity of the pathological manifestations of senile plaque and neurofibrillary tangles in patients with SAD. For example, Kang et al.20 found that patients with the LRP1 C/C genotype had more neuritic plaques and tangles than those with the T/T or T/C genotypes.

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