Non-enzymatically glycated tau in Alzheimer's disease induces neuronal oxidant stress resulting in cytokine gene expression and release of amyloid beta-peptide

Nat Med. 1995 Jul;1(7):693-9. doi: 10.1038/nm0795-693.


Paired helical filament (PHF) tau is the principal component of neurofibrillary tangles, a characteristic feature of the neurodegenerative pathology in Alzheimer's disease (AD). Post-translational modification of tau, especially phosphorylation, has been considered a major factor in aggregation and diminished microtubule interactions of PHF-tau. Recently, it has been recognized that PHF-tau is also subject to non-enzymatic glycation, with formation of advanced glycation end products (AGEs). We now show that as a consequence of glycation, PHF-tau from AD and AGE-tau generate oxygen free radicals, thereby activating transcription via nuclear factor-kappa B, increasing amyloid beta-protein precursor and release of approximately 4 kD amyloid beta-peptides. These data provide insight into how PHF-tau disturbs neuronal function, and add to a growing body of evidence that oxidant stress contributes to the pathogenesis of AD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Amyloid beta-Protein Precursor / biosynthesis*
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Animals, Newborn
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism
  • Cytochrome c Group / metabolism
  • Feedback
  • Gene Expression Regulation*
  • Glycosylation
  • Humans
  • Interleukin-6 / biosynthesis*
  • Interleukin-6 / genetics
  • Neuroblastoma / pathology
  • Oxidative Stress*
  • Protein Processing, Post-Translational*
  • Rats
  • Reactive Oxygen Species / metabolism*
  • Superoxide Dismutase / metabolism
  • Temporal Lobe / metabolism
  • Transfection
  • Tumor Cells, Cultured
  • tau Proteins / chemistry
  • tau Proteins / metabolism*


  • Amyloid beta-Protein Precursor
  • Cytochrome c Group
  • Interleukin-6
  • Reactive Oxygen Species
  • tau Proteins
  • Superoxide Dismutase