Vardy, E.R.L.C, Rice, P.J, Bowie, P.C.W, Holmes, J.D, Grant, P.J and Hooper, N.M (2007) Increased circulating insulin-like growth factor-1 in late-onset Alzheimer's disease. Journal of Alzheimer's Disease, 12 (4). pp. 285-290. ISSN 1387-2877Full text available as:
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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.
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