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AGE

, Volume 11, Issue 4, pp 158–166 | Cite as

Glucose and related brain metabolism in dementia of Alzheimer type and its morphological significance

  • Siegfried Hoyer
Article

Abstract

A unifying hypothesis of the pathobiochemical events leading to cell damage and cell death in DAT brain is advanced. This hypothesis is based upon the early and the most prominent disturbances in the glycolytic glucose breakdown and pyruvate oxidation, associated with an excessive protein catabolism as were found in early-onset DAT. The abnormality in intracellular glucose homeostasis is hypothesized to be caused by a deficiency at the insulin/insulin receptor level of the neuron giving rise to a cascade of cell damaging events. These include the formation of neurotoxic amino acids, disturbance of intracellular Ca2+ homeostasis and the degradation of intracellular components as well as membranes and cell surface receptors. The pathobiochemical changes are related to the morphological hallmarks as are neuronal loss, and the formation of neurofibrillary tangles and neuritic plaques in DAT. It is assumed that neurons equipped with high densities of both insulin receptors and glutamatergic N-methyl-D-aspartate receptors, as is the case in hippocampal and cortical pyramidal cells, are particularly vulnerable and are prone to the formation of abnormal structures, such as neurofibrillary tangles and neuritic plaques, and to cell death.

Keywords

Dementia Neurofibrillary Tangle Alzheimer Type Protein Catabolism Neuritic Plaque 
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.

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Copyright information

© American Aging Association, Inc. 1988

Authors and Affiliations

  • Siegfried Hoyer
    • 1
  1. 1.Department of Pathochemistry and General NeurochemistryUniversity of HeidelbergHeidelbergGermany

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