A validated antibody panel for the characterization of tau post-translational modifications

Mol Neurodegener. 2017 Nov 21;12(1):87. doi: 10.1186/s13024-017-0229-1.


Background: Tau is a microtubule-binding protein, which is subject to various post-translational modifications (PTMs) including phosphorylation, methylation, acetylation, glycosylation, nitration, sumoylation and truncation. Aberrant PTMs such as hyperphosphorylation result in tau aggregation and the formation of neurofibrillary tangles, which are a hallmark of Alzheimer's disease (AD). In order to study the importance of PTMs on tau function, antibodies raised against specific modification sites are widely used. However, quality control of these antibodies is lacking and their specificity for particular modifications is often unclear.

Methods: In this study, we first designed an online tool called 'TauPTM', which enables the visualization of PTMs and their interactions on human tau. Using TauPTM, we next searched for commercially available antibodies against tau PTMs and characterized their specificity by peptide array, immunoblotting, electrochemiluminescence ELISA and immunofluorescence technologies.

Results: We demonstrate that commercially available antibodies can show a significant lack of specificity, and PTM-specific antibodies in particular often recognize non-modified versions of the protein. In addition, detection may be hindered by other PTMs in close vicinity, complicating the interpretation of results. Finally, we compiled a panel of specific antibodies and show that they are useful to detect PTM-modified endogenous tau in hiPSC-derived neurons and mouse brains.

Conclusion: This study has created a platform to reliably and robustly detect changes in localization and abundance of post-translationally modified tau in health and disease. A web-based version of TauPTM is fully available at http://www.tauptm.org .

Keywords: Alzheimer’s disease; Antibody validation; Post-translational modification; Tau.

Publication types

  • Validation Study

MeSH terms

  • Acetylation
  • Animals
  • Antibody Specificity
  • Brain / metabolism
  • Humans
  • Methylation
  • Mice
  • Mice, Transgenic
  • Phosphorylation
  • Protein Processing, Post-Translational*
  • tau Proteins / immunology*
  • tau Proteins / metabolism*


  • tau Proteins