Post-translational modifications of tau protein in Alzheimer's disease

J Neural Transm (Vienna). 2005 Jun;112(6):813-38. doi: 10.1007/s00702-004-0221-0. Epub 2004 Oct 27.


Microtubule-associated protein tau undergoes several post-translational modifications and aggregates into paired helical filaments (PHFs) in Alzheimer's disease (AD) and other tauopathies. These modifications of tau include hyperphosphorylation, glycosylation, ubiquitination, glycation, polyamination, nitration, and proteolysis. Hyperphosphorylation and glycosylation are crucial to the molecular pathogenesis of neurofibrillary degeneration of AD. The others appear to represent failed mechanisms for neurons to remove damaged, misfolded, and aggregated proteins. This review summarizes the abnormal post-translational modifications of tau and discusses the pathophysiological relevance of hyperphosphorylation and glycosylation of tau. Total tau and phosphorylated tau levels in cerebrospinal fluid as a diagnostic biomarkers are also reviewed. Analyses of the current advances in tau modifications suggest that intervention addressing these abnormalities may offer promising therapeutic opportunities to prevent and treat neurofibrillary degeneration of AD and other tauopathies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Animals
  • Biomarkers / analysis
  • Glycosylation
  • Humans
  • Phosphorylation
  • Protein Processing, Post-Translational / physiology*
  • tau Proteins / cerebrospinal fluid
  • tau Proteins / genetics
  • tau Proteins / metabolism*


  • Biomarkers
  • tau Proteins