GLYCOSYLATION OF MICROTUBULE-ASSOCIATED PROTEIN-TAU - AN ABNORMAL POSTTRANSLATIONAL MODIFICATION IN ALZHEIMERS-DISEASE

Alzheimer's disease (AD) is characterized by the presence of numerous neurons with neurofibrillary tangles of paired helical filaments (PHFs ). The microtubule-associated protein tau in abnormally hyperphosphory lated form is the major protein subunit of the PHF. We now show that P HF tangles isolated from AD brains are glycosylated, whereas no glycan is detected in normal tau. Deglycosylation of PHF tangles by endoglyc osidase F/N-glycosidase F converts them into bundles of straight filam ents 2.5 +/- 0.5 nm in diameter, similar to those generated by the int eraction of normal tau and abnormally hyperphosphorylated tau (AD P-ta u). Deglycosylation plus dephosphorylation, but not deglycosylation al one, of AD P-tau and tau from PHF tangles restores their microtubule p olymerization activity. Dephosphorylation of deglycosylated PHF tangle s results in increased tan release. Thus, although the abnormal phosph orylation might promote aggregation of tau and inhibition of the assem bly of microtubules, glycosylation appears to be responsible for the m aintenance of the PHF structure.