Genetic association of low density lipoprotein receptor and Alzheimer's disease

Rangaraj K. Gopalraj, Haiyan Zhu, Jeremiah F. Kelly, Marta Mendiondo, Joseph F. Pulliam, David A. Bennett, Steven Estus

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

The low density lipoprotein receptor (LDLR) is an attractive candidate gene for genetic association with Alzheimer's disease (AD) because: (i) the LDLR is an apolipoprotein E (apoE) receptor, alleles of which have been associated with AD, (ii) LDLR resides at chromosome 19p13.3 within a region linked to AD, and (iii) LDLR modulates the homeostasis of cholesterol, which itself appears associated with AD. Therefore, we evaluated whether LDLR haplotypes alter the odds of AD by performing an association study examining three LDLR single nucleotide polymorphisms (SNPs) in 118 AD patients and 133 non-AD subjects. LDLR genotypes were obtained by TaqMan allelic discrimination assays. Although individual LDLR SNPs were not associated with AD, analyses of unambiguous haplotypes suggested the hypothesis that the 211 LDLR haplotype was associated with reduced odds of AD. We then evaluated this hypothesis in a second study cohort, i.e., the Religious Orders Study. These results supported the hypothesis that the 211 LDLR haplotype is associated with reduced odds of AD. Moreover, these data suggested further associations between LDLR variants and AD. Thus, LDLR variants appear significantly associated with AD and merit additional study.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalNeurobiology of Aging
Volume26
Issue number1
DOIs
StatePublished - Jan 2005

Bibliographical note

Funding Information:
The authors thank the UKY AD Research Center including William Markesbery as well as members of the Estus Laboratory for helpful discussion. This project was funded by NIH (R01AG21545, 2P50AG05144-17, R01AG21362, P30AG10161, and R01AG15819).

Keywords

  • Alzheimer's disease
  • Amyloid beta
  • Cholesterol
  • Genetics
  • LDLR
  • Polymorphism
  • SNP

ASJC Scopus subject areas

  • Neuroscience (all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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