Insulin effects on glucose metabolism, memory, and plasma amyloid precursor protein in Alzheimer's disease differ according to apolipoprotein-E genotype

Ann N Y Acad Sci. 2000 Apr:903:222-8. doi: 10.1111/j.1749-6632.2000.tb06371.x.


Higher fasting plasma insulin levels and reduced CSF-to-plasma insulin ratios, suggestive of insulin resistance, have been observed in patients with Alzheimer's disease (AD) who do not possess an apolipoprotein E (ApoE)-epsilon 4 allele. Insulin has also been implicated in processing of beta-amyloid and amyloid precursor protein (APP). We examined the effects of intravenous insulin administration while maintaining euglycemia on insulin-mediated glucose disposal, memory, and plasma APP in patients with AD and normal adults of varying ApoE genotypes. AD subjects without an epsilon 4 allele had significantly lower insulin-mediated glucose disposal rates than did AD patients with an epsilon 4 allele (p < 0.03) or than did normal adults without an epsilon 4 allele (p < 0.02). AD subjects without an epsilon 4 allele also showed significant memory facilitation with insulin administration (p < 0.04), whereas the AD-epsilon 4 group did not. Insulin reduced APP levels for AD patients without an ApoE epsilon 4 allele, but raised APP for AD patients with an ApoE epsilon H4 allele These results document ApoE-related differences in insulin metabolism in AD that may relate to disease pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Alzheimer Disease / genetics
  • Alzheimer Disease / physiopathology*
  • Alzheimer Disease / psychology
  • Amyloid beta-Protein Precursor / blood*
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Female
  • Genotype
  • Glucose Clamp Technique
  • Humans
  • Insulin / blood*
  • Insulin / pharmacology
  • Insulin Resistance
  • Male
  • Memory / physiology*
  • Reference Values


  • Amyloid beta-Protein Precursor
  • Apolipoprotein E4
  • Apolipoproteins E
  • Blood Glucose
  • Insulin