Glycated tau protein in Alzheimer disease: A mechanism for induction of oxidant stress

S. D. Yan, X. Chen, A. M. Schmidt, J. Brett, G. Godman, Y. S. Zou, C. W. Scott, C. Caputo, T. Frappier, M. A. Smith, G. Perry, S. H. Yen, D. Stern

Research output: Contribution to journalArticle

500 Citations (Scopus)

Abstract

The stability of proteins that constitute the neurofibrillary tangles and senile plaques of Alzheimer disease suggests that they would be ideal substrates for nonenzymatic glycation, a process that occurs over long times, even at normal levels of glucose, ultimately resulting in the formation of advanced glycation end products (AGEs). AGE-modified proteins aggregate, and they generate reactive oxygen intermediates. Using monospecific antibody to AGEs, we have colocalized these AGEs with paired helical filament tau in neurofibrillary tangles in sporadic Alzheimer disease. Such neurons also exhibited evidence of oxidant stress: induction of malondialdehyde epitopes and heme oxygenase 1 antigen. AGE-recombinant tau generated reactive oxygen intermediates and, when introduced into the cytoplasm of SH-SY5Y neuroblastoma cells, induced oxidant stress. We propose that in Alzheimer disease, AGEs in paired helical filament tau can induce oxidant stress, thereby promoting neuronal dysfunction.

Original languageEnglish (US)
Pages (from-to)7787-7791
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number16
DOIs
StatePublished - Aug 2 1994
Externally publishedYes

Fingerprint

tau Proteins
Oxidants
Alzheimer Disease
Neurofibrillary Tangles
Oxygen
Advanced Glycosylation End Products
Heme Oxygenase-1
Protein Stability
Amyloid Plaques
Malondialdehyde
Neuroblastoma
Epitopes
Cytoplasm
Neurons
Antigens
Glucose
Antibodies

Keywords

  • glycation
  • neuron
  • reactive oxygen intermediate

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Glycated tau protein in Alzheimer disease : A mechanism for induction of oxidant stress. / Yan, S. D.; Chen, X.; Schmidt, A. M.; Brett, J.; Godman, G.; Zou, Y. S.; Scott, C. W.; Caputo, C.; Frappier, T.; Smith, M. A.; Perry, G.; Yen, S. H.; Stern, D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 16, 02.08.1994, p. 7787-7791.

Research output: Contribution to journalArticle

Yan, SD, Chen, X, Schmidt, AM, Brett, J, Godman, G, Zou, YS, Scott, CW, Caputo, C, Frappier, T, Smith, MA, Perry, G, Yen, SH & Stern, D 1994, 'Glycated tau protein in Alzheimer disease: A mechanism for induction of oxidant stress', Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 16, pp. 7787-7791. https://doi.org/10.1073/pnas.91.16.7787
Yan, S. D. ; Chen, X. ; Schmidt, A. M. ; Brett, J. ; Godman, G. ; Zou, Y. S. ; Scott, C. W. ; Caputo, C. ; Frappier, T. ; Smith, M. A. ; Perry, G. ; Yen, S. H. ; Stern, D. / Glycated tau protein in Alzheimer disease : A mechanism for induction of oxidant stress. In: Proceedings of the National Academy of Sciences of the United States of America. 1994 ; Vol. 91, No. 16. pp. 7787-7791.
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