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

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.