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.


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.
Vardy
Emma R L C
ER
Academic Unit of Molecular Vascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, LS2 9JT, UK.
Rice
Penny J
PJ
Bowie
Peter C W
PC
Holmes
John D
JD
Grant
Peter J
PJ
Hooper
Nigel M
NM
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
D001057:Apolipoproteins E; C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I