title: Increased circulating insulin-like growth factor-1 in late-onset Alzheimer's disease.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Academic Unit of Molecular Vascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Emma R L C
authors.initials: ER
authors.lastname: Vardy
authors.forename: Penny J
authors.initials: PJ
authors.lastname: Rice
authors.forename: Peter C W
authors.initials: PC
authors.lastname: Bowie
authors.forename: John D
authors.initials: JD
authors.lastname: Holmes
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Grant
authors.forename: Nigel M
authors.initials: NM
authors.lastname: Hooper
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D001057:Apolipoproteins E / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood* / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male
chemical_list: D001057:Apolipoproteins E; C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I