Journal of Neural Transmission

, Volume 109, Issue 7, pp 991–1002

The aging brain. Changes in the neuronal insulin/insulin receptor signal transduction cascade trigger late-onset sporadic Alzheimer disease (SAD). A mini-review

  • S. Hoyer

DOI: 10.1007/s007020200082

Cite this article as:
Hoyer, S. J Neural Transm (2002) 109: 991. doi:10.1007/s007020200082

Summary.

Aging of the brain has been demonstrated to be the main risk factor for late-onset sporadic AD what is in contrast to early-onset familial AD in which mutations predominante the pathology. Aging of the brain was found to be associated with a multitude of aberrancies from normal in morphological, cellular and molecular terms. Recent findings provide clear evidence that the function of the neuronal insulin/insulin receptor signal transduction cascade is of pivotal significane to maintain normal cerebral blood flow and oxidative energy metabolism, work of the endoplasmatic reticulum/Golgi apparatus and the cell cycle in terminally differentiated neurons no longer in the cell cycle. It has become evident that normal metabolism of both amyloid precursor protein and tau-protein is part of interactive processes controlled by the neuronal I/IR signal transduction cascade. In normal brain aging, the function of this cascade starts to fail compared to normal resulting in adverse effects in CBF/oxidative energy metabolism, work of the endoplasmatic reticulum/Golgi apparatus and cell cycle. The aberrancies may not be drastic, but multifold and permanently existing, inclusive the metabolism of APP and tau-protein. The amount of intraneuronally formed βA4 may increase, and tau-protein may become hyperphosphorylated. These processes as a whole may increase the vulnarability of the aging brain and may facilitate the generatin of late-onset sporadic AD.

Keywords: Agingbraininsulininsulin receptoramyloid precursor proteintau-protein.

Copyright information

© Springer-Verlag Wien 2002

Authors and Affiliations

  • S. Hoyer
    • 1
  1. 1.Department of Pathochemistry and General Neurochemistry, Institute of Pathology, University of Heidelberg, Federal Republic of GermanyDE