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Glycosylation of microtubule–associated protein tau: An abnormal posttranslational modification in Alzheimer's disease

Nature Medicine volume 2, pages 871–875 (1996)Cite this article

Abstract

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 hyperphosphorylated form is the major protein subunit of the PHF. We now show that PHF tangles isolated from AD brains are glycosylated, whereas no glycan is detected in normal tau. Deglycosylation of PHF tangles by endoglycosidase F/N–glycosidase F converts them into bundles of straight filaments 2.5 ± 0.5 nm in diameter, similar to those generated by the interaction of normal tau and abnormally hyperphosphorylated tau (AD P–tau). Deglycosylation plus dephosphorylation, but not deglycosylation alone, of AD P–tau and tau from PHF tangles restores their microtubule polymerization activity. Dephosphorylation of deglycosylated PHF tangles results in increased tau release. Thus, although the abnormal phosphorylation might promote aggregation of tau and inhibition of the assembly of microtubules, glycosylation appears to be responsible for the maintenance of the PHF structure.

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Authors and Affiliations

  1. New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, 10314, USA

    Jian-Zhi Wang, Inge Grundke-Iqbal & Khalid Iqbal

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  1. Jian-Zhi Wang
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Wang, JZ., Grundke-Iqbal, I. & Iqbal, K. Glycosylation of microtubule–associated protein tau: An abnormal posttranslational modification in Alzheimer's disease. Nat Med 2, 871–875 (1996). https://doi.org/10.1038/nm0896-871

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