Insulin degrading enzyme (IDE) genetic variants and risk of Alzheimer's disease: Evidence of effect modification by apolipoprotein E (APOE)

S. D. Edland, F. Wavrant-De Vriesé, D. Compton, G. E. Smith, R. Ivnik, B. F. Boeve, E. G. Tangalos, R. C. Petersen

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Abstract

Insulin degrading enzyme (IDE) is a protease that degrades insulin and the β-amyloid peptide implicated in Alzheimer's disease (AD). We reexamined data on five previously reported IDE polymorphisms stratifying the analysis by the presence or absence of an apolipoprotein E (APOE) ε4 allele. Three IDE variants were associated with AD within ε4-negative subjects (genotype exact test P-values ≤0.02). A haplotype containing the minor variant at each of these sites represented an estimated 4.2% of case haplotypes versus 12.3% of control haplotypes among ε4-negative subjects. Lack of this minor haplotype may be predictive of AD, potentially explaining some fraction of disease within subjects without the APOE ε4 risk allele. Confirmation of this finding with a larger sample of cases and controls is warranted.

Original languageEnglish (US)
Pages (from-to)21-24
Number of pages4
JournalNeuroscience Letters
Volume345
Issue number1
DOIs
StatePublished - Jul 10 2003

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Keywords

  • Alzheimer's disease
  • Amyloid beta
  • Genetic epidemiology
  • Insulin degrading enzyme
  • Protease

ASJC Scopus subject areas

  • Neuroscience(all)

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