TAU-PROTEIN FROM ALZHEIMERS-DISEASE PATIENTS IS GLYCATED AT ITS TUBULIN-BINDING DOMAIN

Glycated residues of tau protein from paired helical filaments isolate d from the brains of Alzheimer's disease patients were localized by do ing a proteolytic cleavage of the protein, fractionation of the result ing peptides, and identification of those peptides using specific anti bodies. The most suitable residues for glycation, lysines, present at the tubulin-binding motif of tau protein, seem to be preferentially mo dified compared with those lysines present at other regions. Among the se modified lysines, those located in the sequence comprising residues 318-336 (in the largest human tau isoform) were found to be glycated, as determined by the reaction with an antibody that recognizes a glyc ated peptide containing this sequence. Because those lysines are prese nt in a tubulin binding motif of tau protein, its modification could r esult in a decrease in the interaction of tau with tubulin.