GLYCATED TAU-PROTEIN IN ALZHEIMER-DISEASE - A MECHANISM FOR INDUCTIONOF OXIDANT STRESS

The stability of proteins that constitute the neurofibrillary tangles and senile plaques of Alzheimer disease suggests that they would be id eal 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. U sing monospecific antibody to AGEs, we have colocalized these AGEs wit h paired helical filament tau in neurofibrillary tangles in sporadic A lzheimer disease. Such neurons also exhibited evidence of oxidant stre ss: induction of malondialdehyde epitopes and heme oxygenase 1 antigen . AGE-recombinant tau generated reactive oxygen intermediates and, whe n introduced into the cytoplasm of SH-SY5Y neuroblastoma cells, induce d oxidant stress. We propose that in Alzheimer disease, AGEs in paired helical filament tau can induce oxidant stress, thereby promoting neu ronal dysfunction.