An immunochemical study on tau glycation in paired helical filaments

Li Wen Ko, Eric C. Ko, Parimala Nacharaju, Wan Kyng Liu, Emmanuel Chang, Agnes Kenessey, Shu Hui C Yen

Research output: Contribution to journalArticle

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Abstract

Glycation is a non-enzymatic posttranslational modification that involves a covalent linkage between a sugar and an amino group of protein molecule forming ketoamine. Subsequent oxidation, fragmentation and/or crosslinking of ketoamine leads to the production of advanced glycation endproducts (AGEs). Formation of AGEs causes detrimental effects on the structure and function of affected proteins. Accumulation of AGEs has been implicated in normal aging and in the pathogenesis of diabetes-associated complications and Alzheimer's disease (AD). Of all AGEs, N(ε)- (carboxymethyl)lysine (CML) is a major glycoxidation product known to be stable and accumulate progressively in vivo. In order to determine if tau is glycated in AD, we raised a rabbit antibody to CML that demonstrated its usefulness in detecting glycation of different proteins in vitro, including BSA, ribonuclease, lysozyme and recombinant tau. Immunochemical analyses indicated that ribose and glucose-6-phosphate are more effective than glucose in generating CML formation in these proteins. We used this antibody to probe for glycation in the following human tau preparations: tau of normal brains and preparations of soluble PHF-tau as well as insoluble PHF from AD brains. All three principal tau components resolved from PHF-tau on Western blots showed CML immunoreactivity indicating that tau is glycated in PHF-tau; and insoluble PHF exhibited prominent CML immunoreactivity on top of the stacking gel. Moreover, immunoelectron microscopic analyses indicate that the anti- CML antibody labels predominantly PHF in aggregates. Taken together, these results suggest that tau becomes glycated in PHF-tau and glycation may play a role in stabilizing PHF aggregation leading to tangle formation in AD.

Original languageEnglish (US)
Pages (from-to)301-313
Number of pages13
JournalBrain Research
Volume830
Issue number2
DOIs
StatePublished - Jun 5 1999

Fingerprint

Alzheimer Disease
Antibodies
Proteins
Amino Sugars
Glucose-6-Phosphate
Ribose
Brain
Diabetes Complications
Post Translational Protein Processing
Ribonucleases
Muramidase
N(6)-carboxymethyllysine
Western Blotting
Gels
Rabbits
Glucose

Keywords

  • Alzheimer's disease
  • Glycation
  • PHF
  • Tau

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Ko, L. W., Ko, E. C., Nacharaju, P., Liu, W. K., Chang, E., Kenessey, A., & Yen, S. H. C. (1999). An immunochemical study on tau glycation in paired helical filaments. Brain Research, 830(2), 301-313. https://doi.org/10.1016/S0006-8993(99)01415-8

An immunochemical study on tau glycation in paired helical filaments. / Ko, Li Wen; Ko, Eric C.; Nacharaju, Parimala; Liu, Wan Kyng; Chang, Emmanuel; Kenessey, Agnes; Yen, Shu Hui C.

In: Brain Research, Vol. 830, No. 2, 05.06.1999, p. 301-313.

Research output: Contribution to journalArticle

Ko, LW, Ko, EC, Nacharaju, P, Liu, WK, Chang, E, Kenessey, A & Yen, SHC 1999, 'An immunochemical study on tau glycation in paired helical filaments', Brain Research, vol. 830, no. 2, pp. 301-313. https://doi.org/10.1016/S0006-8993(99)01415-8
Ko LW, Ko EC, Nacharaju P, Liu WK, Chang E, Kenessey A et al. An immunochemical study on tau glycation in paired helical filaments. Brain Research. 1999 Jun 5;830(2):301-313. https://doi.org/10.1016/S0006-8993(99)01415-8
Ko, Li Wen ; Ko, Eric C. ; Nacharaju, Parimala ; Liu, Wan Kyng ; Chang, Emmanuel ; Kenessey, Agnes ; Yen, Shu Hui C. / An immunochemical study on tau glycation in paired helical filaments. In: Brain Research. 1999 ; Vol. 830, No. 2. pp. 301-313.
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