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.
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.
Authors: Robert Winker; Ina Lukas; Thomas Perkmann; Helmut Haslacher; Elisabeth Ponocny; Johann Lehrner; Dimiter Tscholakoff; Peter Dal-Bianco Journal: Wien Klin Wochenschr Date: 2010-11-15 Impact factor: 1.704
Authors: Kendra L Puig; Joshua A Kulas; Whitney Franklin; Sharlene G Rakoczy; Giulio Taglialatela; Holly M Brown-Borg; Colin K Combs Journal: Neurobiol Aging Date: 2016-01-06 Impact factor: 4.673