[New hypothesis on etiopathogenesis of Alzheimer syndrome. Advanced glycation end products (AGEs)]

Nervenarzt. 1996 Nov;67(11):924-9. doi: 10.1007/s001150050073.
[Article in German]

Abstract

Despite intense efforts, it has not yet been possible to clarify the etiopathogenesis of Alzheimer's dementia. There are, however, hypotheses which focus on certain aspects of this type of dementia, characterized by particular neuropathological alterations and clinical correlates. Recently, evidence has accumulated that advanced glycation endproducts (AGEs) could play an important role in the etiology of the Alzheimer's syndrome. AGEs are generated by an irreversible reaction through the non-enzymatic, long-term glycosylation of proteins. They are strongly resistant to proteolytic processes and induce protein crosslinking. They could thus inhibit the physiological functions of many proteins. Moreover, it is suggested that they contribute to the transformation of the soluble form of beta-amyloid into its unsoluble version. AGEs are also demonstrable in neurofibrillary tangles (NFTs). A further mechanism by which AGEs might be pathogenic is via their induction of oxidative stress. AGEs probably exert their pathological effects not only directly because of their chemical properties, but also by indirect receptor-mediated mechanisms. Further investigation of AGE-mediated mechanisms should reveal their role in the etiopathogenesis of the Alzheimer's syndrome and, finally, lead to the development of new pharmacological strategies aimed at inhibiting protein cross-linking.

Publication types

  • Review

MeSH terms

  • Aged
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Protein Precursor / metabolism
  • Brain / pathology
  • Brain / physiopathology
  • Glycation End Products, Advanced / physiology*
  • Humans
  • Neurofibrillary Tangles / pathology
  • Neurofibrillary Tangles / physiology
  • Reactive Oxygen Species / metabolism

Substances

  • Amyloid beta-Protein Precursor
  • Glycation End Products, Advanced
  • Reactive Oxygen Species