Increased circulating insulin-like growth factor-1 in late-onset Alzheimer's disease

J Alzheimers Dis. 2007 Dec;12(4):285-90. doi: 10.3233/jad-2007-12401.


Background: Insulin-like growth factor (IGF)-1 has been implicated in the pathogenesis of Alzheimer's disease (AD).

Methods: We compared the level of circulating total and bioavailable IGF-1, by simultaneous measurements of IGF-1 and IGF binding protein (IGFBP)-3, between 87 patients diagnosed with AD and 126 age and sex matched control subjects without cognitive impairment. Blood samples were collected and IGF-1 and IGFBP-3 measured by ELISA. Subjects were also genotyped for apolipoprotein E.

Results: Total circulating IGF-1 levels were significantly raised in the AD group as compared to the control group (p=0.022). There was no significant difference in the circulating level of IGFBP-3 between the two groups. When the IGF-1 levels were ratioed against IGFBP-3 levels as an indicator of unbound, bioavailable circulating IGF-1, there was a significant increase in the molar IGF-1:IGFBP-3 ratio in the AD subjects (0.181 +/- 0.006) as compared to the controls (0.156 +/- 0.004) (p< 0.001). Logistic regression analysis revealed that an increase in the IGF-1:IGFBP-3 molar ratio increased the risk of AD significantly.

Conclusion: The results of increased total and free circulating IGF-1 support the hypothesis that in its early stages late-onset AD reflects a state of resistance to IGF-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease* / blood
  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / physiopathology
  • Apolipoproteins E / blood
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Insulin Resistance / physiology
  • Insulin-Like Growth Factor Binding Protein 1 / blood*
  • Insulin-Like Growth Factor Binding Protein 1 / genetics*
  • Insulin-Like Growth Factor I / metabolism*
  • Male


  • Apolipoproteins E
  • IGFBP1 protein, human
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor I