Binding of [125I]-Insulin-Like Growth Factor-1 (IGF-1) in Brains of Alzheimer’s and Alcoholic Patients

  • Fulton T. Crews
  • R. McElhaney
  • G. Freund
  • W. E. Ballinger
  • Don W. Walker
  • Bruce E. Hunter
  • Mohan K. Raizada
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 293)


Patients with chronic alcoholism and/or Alzheimer’s disease suffer from degenerative changes in the cerebral cortex and hippocampus. To investigate possible changes in IGF-1 receptor binding sites in brain tissue of patients with these pathological conditions, the binding of [125I]-IGF-1 was determined in tissues obtained from control, Alzheimer’s and/or patients with a history of alcoholism. The four experimental groups examined consisted of patients from similar age groups. Specific binding of [125I]-IGF-1 to cerebral cortical membranes from Alzheimer’s patients had significantly more binding sites than age-matched controls, alcoholic patients and alcoholic patients with Alzheimer’s disease. Regression analyses indicated that there were no significant differences in [125I]-IGF-1 binding in cerebral cortex with regard to age of patients (1.1% of total variance with a range of 52 to 92 years). Likewise, the time interval between death and autopsy contributed only 1.4% to the total variance in IGF-1 binding. No statistical differences in [125I]-IGF-1 binding were noted in hippocampal tissue from the various patient groups. Thus, human IGF-1 binding sites in cerebral cortex and hippocampus appear to be relatively stable for a number of variables. The increase in cerebral cortical [125I]-IGF-1 binding sites could be due to upregulation of IGF-1 receptors resulting from a decrease in IGF-1 levels in Alzheimer’s patients.


Cerebral Cortex Alcoholic Patient Nerve Growth Factor Receptor Intrinsic Tyrosine Kinase Activity Hippocampal Membrane 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Adamo, M., Raizada, M.K. and LeRoith, D. (1989) Insulin and insulin-like growth factor receptors in the nervous system. Mol. Neurobiol. 3:71–100.PubMedCrossRefGoogle Scholar
  2. 2.
    Masters, B.A., Shemer, J., LeRoith, D. and Raizada, M.K. (1989) Insulin-like growth factor receptors in the central nervous system: Phosphorylation events and cellular mediators of biological function. In: Molecular and Cellular Biology of IGFs and Their Receptors ,D. LeRoith and M.K. Raizada, eds., Plenum Press, New York, pp. 341–358.Google Scholar
  3. 3.
    Giacobini, M.M., Olson, L, Hoffer, B.J. and Sara, V.R. (1990) Truncated IGF-1 exerts trophic effects on fetal brain tissue grafts. Exp. Neurol. 108(1):33–37.PubMedCrossRefGoogle Scholar
  4. 4.
    Recio, P.E. and Ishii, D.N. (1988) Insulin and insulin-like growth factor receptors regulating neurite formation in cultured human neuroblastoma cells. J. Neurosci. Res. 19(3) :312–320.CrossRefGoogle Scholar
  5. 5.
    Gammeltoft, S., Haselbacher, G.K., Humbel, R.E., Fehlmann, M. and Van, O.E. (1985) Two types of receptor for insulin-like growth factors in mammalian brain. Embo. J. 4(13A):3407–3412.PubMedGoogle Scholar
  6. 6.
    Sara, V.R., Hall, K., Von, H.H., Humbel, R., Sjogren, B. and Wetterbergn, L. (1982) Evidence for the presence of specific receptors for insulin-like growth factors 1 (IGF-1) and 2 (IGF-2) and insulin throughout the adult human brain. Neurosci. Lett. 34(1):39–44.PubMedCrossRefGoogle Scholar
  7. 7.
    Thienhaus, O.J., Hartford, J.H., Skelly, M.F. and Bosmann, H.B. (1985) Biologic markers in Alzheimer’s disease. J. Am. Geriatr. Soc. 33(10):715–726.PubMedGoogle Scholar
  8. 8.
    Reubi, J.C. and Palacios, J. (1986) Somatostatin and Alzheimer’s disease: A hypothesis. J. Neurol. 233(6):370–372.PubMedCrossRefGoogle Scholar
  9. 9.
    Freund, G. and Ballinger, W.E., Jr. (1988) Decrease of benzodiazepine receptors in frontal cortex of alcoholics. Alcohol 5:275–282.PubMedCrossRefGoogle Scholar
  10. 10.
    Freund, G. and Ballinger, W.E., Jr. (1989) Loss of muscarinic cholinergic receptors from temporal cortex of alcohol abusers. Metabolic Brain Disease 4:121–141.PubMedCrossRefGoogle Scholar
  11. 11.
    Freund, G. and Ballinger, W.E., Jr. (1988) Loss of cholinergic muscarinic receptors in the frontal cortex of alcohol abusers. Alcoholism: Clinic. Exp. Research 12:630–638.CrossRefGoogle Scholar
  12. 12.
    Lowry, O.H., Rosebrough, N.J., Fan, A.J. and Randall, R.J. (1951) Protein measurement with the folin phenol reagent. J. Biol. Chem. 193:265–275.PubMedGoogle Scholar
  13. 13.
    Shemer, J., Raizada, M.K., Masters, B.A., Ota, A. and LeRoith, D. (1987) Insulin-like growth factor 1 receptors in neuronal and glial cells: Characterization and biological effects in primary culture. J. Biol. Chem. 262(16):7693–7699.PubMedGoogle Scholar
  14. 14.
    Masters, B.A., Werner, H., Roberts, C.T., Jr., LeRoith, D. and Raizada, M.K. (1991) Developmental regulation of insulin-like growth factor 1 stimulated glucose transporter in rat brain astrocytes. Endocrinology (in press).Google Scholar
  15. 15.
    Masters, B.A., Werner, H., Roberts, C.T., Jr., LeRoith, D. and Raizada, M.K. (1991) Insulin-like growth factor 1 receptors and IGF-1 actions in oligodendrocytes from rat brain. Regulatory Peptides (in press).Google Scholar
  16. 16.
    Raizada, M.K. (1991) Insulin-like growth factor 1 in the brain: A possible modulator of intercellular communication. In: Molecular Biology and Physiology of Insulin and Insulin-like Growth Factors ,M.K. Raizada and D. LeRoith, eds., Plenum Press, New York (in press).Google Scholar
  17. 17.
    Nilsson, L, Sara, V.R., and Nordberg, A. (1988) Insulin-like growth factor 1 stimulates the release of acetylcholine from rat cortical slices. Neurosci. Lett. 88:221–226.PubMedCrossRefGoogle Scholar
  18. 18.
    Knusel, B., Michel, P.P., Schwaber, J.S., and Hefti, F. (1991) Selective and non-selective stimulation of central cholinergic and dopaminergic development in vitro by nerve growth factor, basic fibroblast growth factor, epidermal growth factor, insulin and the insulin-like growth factors I and II. Dev. Neurosci. (in press).Google Scholar
  19. 19.
    LeRoith, D., Shemer, J., Adamo, M., Raizada, M.K., Heffez, D. and Zick, Y. (1989) Insulin and IGF-I stimulate phosphorylation of their respective receptors in intact neuronal and glial cells in primary culture. J. Mol. Neurosci. 1(1):3–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Hefti, F., and Mash, D. (1989) Localization of nerve growth factor receptors in the normal human brain and in Alzheimer’s disease. Neurobiol. of Aging 10:75–87.CrossRefGoogle Scholar
  21. 21.
    Higgins, G., and Mufson, E.J. (1989) NGF receptor gene expression is decreased in the nucleus basalis in Alzheimer’s disease. Exp. Neurology 106:222–236.CrossRefGoogle Scholar
  22. 22.
    Mufson, E.J., Bothwell, M., and Kordower, J. H. (1989) Loss of nerve growth factor receptor-containing neurons in Alzheimer’s disease: A quantitative analysis across subregions of the basal forebrain. Exp. Neurology 105:221–232.CrossRefGoogle Scholar
  23. 23.
    Whitehouse, P.J. (1987) Neurotransmitter receptor alterations in Alzheimer’s disease: A review. Alzheimer Dis. Assoc. Disord. 1(1):9–18.PubMedCrossRefGoogle Scholar
  24. 24.
    Sara, V.R., Hall, K., Enzell, K., Gardner, A., Morawski, R. and Wetterberg, L. (1982) Somatomedins in aging and dementia disorders of the Alzheimer type. Neurobiol. of Aging 3:117–120.CrossRefGoogle Scholar
  25. 25.
    Sonntag, W.E. and Boyd, R.L. (1988) Chronic ethanol feeding inhibits plasma levels of insulin-like growth factor-1. Life Sciences 43:1325–1330.PubMedCrossRefGoogle Scholar
  26. 26.
    Gonzales, R.A., Ganz, N. and Crews, FT. (1987) Variations in membrane sensitivity of brain region synaptosomes to the effects of ethanol in-vitro and chronic in-vivo treatment. J. Neurochem. 49:158–162.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Fulton T. Crews
    • 1
  • R. McElhaney
    • 1
  • G. Freund
    • 2
  • W. E. Ballinger
    • 3
  • Don W. Walker
    • 4
  • Bruce E. Hunter
    • 4
  • Mohan K. Raizada
    • 5
  1. 1.Department of Pharmacology and Therapeutics (F.T.C., R.M.)University of Florida College of MedicineGainesvilleUSA
  2. 2.Department of Medicine (G, F)University of Florida College of MedicineGainesvilleUSA
  3. 3.Department of Pathology (W.E.B.)University of Florida College of MedicineGainesvilleUSA
  4. 4.Department of Neuroscience (D.W.W., B.E.H.)University of Florida College of MedicineGainesvilleUSA
  5. 5.Department of Physiology (M.K.R.)University of Florida College of MedicineGainesvilleUSA

Personalised recommendations