title: Insulin-degrading enzyme haplotypes affect insulin levels but not dementia risk.
abstract: BACKGROUND
  Insulin-degrading enzyme (IDE) polymorphism is hypothesized to regulate insulin levels as well as processes involved in neuronal compromise found in dementia.
  
  
  METHODS
  We examined the association of IDE haplotypes with dementia and insulin levels in a single well-characterized cohort of Japanese-American men born between 1900 and 1919 and followed since 1965. In 1991, a fasting insulin was obtained; dementia cases were ascertained in 1991 and 1994 in a multi-stage procedure, diagnoses were made according to international guidelines. Five single-nucleotide polymorphisms were genotyped and used for haplotype analysis in a sample of 179 Alzheimer's disease cases, 104 vascular dementia cases and 516 controls nested in the total cohort.
  
  
  RESULTS
  The global test for the haplotype effect on insulin levels was significant (p < 0.0001), adjusting for age, education, apolipoprotein epsilon4 status and fasting glucose.
  
  
  CONCLUSIONS
  There was no association of IDE haplotypes with the risk of dementia. This study suggests IDE may be indirectly related to dementia via its regulation of insulin levels, but it is not a major gene for Alzheimer's.
authors.affiliation: Laboratorie of Neurogenetics, Intramural Research Program, National Institute on Aging, Bethesda, MD 20892, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Marlowe
authors.forename: Rita
authors.initials: R
authors.lastname: Peila
authors.forename: Kelly Suzanne
authors.initials: KS
authors.lastname: Benke
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Lon R
authors.initials: LR
authors.lastname: White
authors.forename: Lenore J
authors.initials: LJ
authors.lastname: Launer
authors.forename: Amanda
authors.initials: A
authors.lastname: Myers
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D015331:Cohort Studies; D015140:Dementia, Vascular / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000097:blood*; D007339:Insulysin / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D007328:Insulin; D007339:Insulysin