Affiliations: [a] Academic Unit of Molecular Vascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, LS2 9JT, UK | [b] Sheffield Care Trust, Grenoside Grange Hospital, Salt Box Lane, Sheffield, S35 8QS, UK | [c] Academic Unit of Psychiatry and Behavioural Sciences, University of Leeds, Leeds, LS2 9JT, UK | [d] Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, and Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, LS2 9JT, UK
Correspondence:
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Corresponding author: Nigel M. Hooper, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, LIGHT Laboratories, Clarendon Way, University of Leeds, Leeds, LS2 9JT, UK. Tel.: +44 113 343 3163; Fax: +44 113 343 6603; E-mail: [email protected].
Note: [] Communicated by Suzanne de la Monte
Abstract: 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.
