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. 1994 Aug 2;91(16):7787–7791. doi: 10.1073/pnas.91.16.7787

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

S D Yan 1, X Chen 1, A M Schmidt 1, J Brett 1, G Godman 1, Y S Zou 1, C W Scott 1, C Caputo 1, T Frappier 1, M A Smith 1, et al.
PMCID: PMC44487  PMID: 8052661

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.

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