Genetic association of the very low density lipoprotein (VLDL) receptor gene with sporadic Alzheimer's disease

Nat Genet. 1995 Oct;11(2):207-9. doi: 10.1038/ng1095-207.


A specific isoform of apolipoprotein E has been associated with the accelerated rate of disease expression of sporadic Alzheimer's disease (AD) and late-onset familial AD (FAD). An earlier age at onset has also been demonstrated in familial AD patients with mutations in the amyloid precursor protein (APP) gene (APP717 and APP670/671)13 carrying the APOE epsilon-4 allele compared to those who do not, but not in familial AD patients with APP692 or 693 mutations, or in chromosome 14-linked familial AD patients. Hypothesizing that receptors for apoE-containing lipoproteins act as a potential risk factor for AD, we performed an association study using a polymorphic triplet (CGG) repeat in the gene for the VLDL receptor (VLDL-R), a receptor for apoE-containing lipoproteins. The frequency of the 5-repeat allele was significantly higher in all of the Japanese sporadic AD patients (P < 0.02) than in the Japanese controls. Moreover, the odds ratio was significantly increased in the AD patients homozygous for the 5-repeat allele (OR = 2.1, 95% CI = [1.1-4.2]). Multiple logistic regression analysis reveals that the relative risk conferred by the presence of two copies of the 5-repeat allele and at least one copy of the APOE epsilon-4 allele is 8.7 (95% CI = [2.9-25.8]). Our results suggest that the VLDL-R gene is a susceptibility gene for AD.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / genetics*
  • Apolipoproteins E / genetics
  • Base Sequence
  • Cerebral Cortex / metabolism
  • Chromosomes, Human, Pair 14*
  • DNA Primers
  • Humans
  • Japan
  • Molecular Sequence Data
  • Odds Ratio
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Receptors, LDL / genetics*
  • Reference Values
  • Regression Analysis
  • Repetitive Sequences, Nucleic Acid*
  • Risk Factors


  • Apolipoproteins E
  • DNA Primers
  • Receptors, LDL
  • VLDL receptor