Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease (original) (raw)

Summary.

The search for the causes of neurodegenerative disorders is a major theme in brain research. Acquired disturbances of several aspects of cellular metabolism appear pathologically important in sporadic Alzheimer's disease (SDAT). Among these brain glucose utilisation is reduced in the early stages of the disease and the regulatory enzymes important for glucose metabolism are reduced. In the brain, insulin, insulin-like growth factors and their receptors regulate glucose metabolism and promote neuronal growth. To detect changes in the functional activity of the brain insulin neuromodulatory system of SDAT patients, we determined the concentrations of insulin and c-peptide as well as insulin receptor binding and IGF-I receptor binding in several regions of postmortem brain cortex during aging and Alzheimer's disease. Additionally, we performed immunohistochemical staining with antibodies against insulin in neocortical brain areas in SDAT and controls. We show for the first time that insulin and c-peptide concentration in the brain are correlated and decrease with aging, as do brain insulin receptor densities. Weak insulin-immunoreactivity could be demonstrated histochemically in pyramidal neurons of controls, whereas in SDAT a stronger insulin-immunoreactivity was found. On a biochemical level, insulin and c-peptide levels were reduced compared to middle-aged controls, but were unchanged compared to age-matched controls. Brain insulin receptor densities in SDAT were decreased compared to middle-aged controls, but increased in comparison to age-matched controls. IGF-I receptor densities were unchanged in aging and in SDAT. Tyrosine kinase activity, a signal transduction mechanism common to both receptor systems, was reduced in SDAT in comparison to middle-aged and age-matched control groups. These data are consistent with a neurotrophic role of insulin in the human brain and a disturbance of insulin signal transduction in SDAT brain and favor the hypothesis that insulin dependent functions may be of pathogenetic relevance in sporadic SDAT.

Access this article

Log in via an institution

Subscribe and save

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Author information

Authors and Affiliations

  1. Department of Psychiatry I, University of Frankfurt/Main,, , , , ,
    L. Frölich
  2. Department of Psychiatry, University of Würzburg,, , , , ,
    D. Blum-Degen, S. Engelsberger, J. Humrich, S. Laufer, D. Muschner, A. Thalheimer, A. Türk & P. Riederer
  3. Department of Psychiatry, University of Magdeburg,, , , , ,
    H.-G. Bernstein
  4. Department of Pathochemistry and General Neurochemistry, University of Heidelberg, Federal Republic of Germany, , , , , , DE
    S. Hoyer
  5. NÖ Landesnervenklinik, Mauer/Amstetten, and, , , , ,
    R. Zöchling & K. W. Boissl
  6. L. Boltzmann Institute of Clinical Neurobiology, Vienna, Austria, , , , , , AT
    K. Jellinger

Authors

  1. L. Frölich
    You can also search for this author inPubMed Google Scholar
  2. D. Blum-Degen
    You can also search for this author inPubMed Google Scholar
  3. H.-G. Bernstein
    You can also search for this author inPubMed Google Scholar
  4. S. Engelsberger
    You can also search for this author inPubMed Google Scholar
  5. J. Humrich
    You can also search for this author inPubMed Google Scholar
  6. S. Laufer
    You can also search for this author inPubMed Google Scholar
  7. D. Muschner
    You can also search for this author inPubMed Google Scholar
  8. A. Thalheimer
    You can also search for this author inPubMed Google Scholar
  9. A. Türk
    You can also search for this author inPubMed Google Scholar
  10. S. Hoyer
    You can also search for this author inPubMed Google Scholar
  11. R. Zöchling
    You can also search for this author inPubMed Google Scholar
  12. K. W. Boissl
    You can also search for this author inPubMed Google Scholar
  13. K. Jellinger
    You can also search for this author inPubMed Google Scholar
  14. P. Riederer
    You can also search for this author inPubMed Google Scholar

Additional information

Accepted November 11, 1997; received August 4, 1997

Rights and permissions

About this article

Cite this article

Frölich, L., Blum-Degen, D., Bernstein, HG. et al. Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease.J Neural Transm 105, 423–438 (1998). https://doi.org/10.1007/s007020050068

Download citation