Phosphorylation of tau protein as the link between oxidative stress, mitochondrial dysfunction, and connectivity failure: implications for Alzheimer's disease

Oxid Med Cell Longev. 2013;2013:940603. doi: 10.1155/2013/940603. Epub 2013 Jul 10.


Alzheimer's disease (AD) is defined by the concurrence of abnormal aggregates composed of phosphorylated tau protein and of abnormal cellular changes including neurite degeneration, loss of neurons, and loss of cognitive functions. While a number of mechanisms have been implicated in this complex disease, oxidative stress remains one of the earliest and strongest events related to disease progression. However, the mechanism that links oxidative stress and cognitive decline remains elusive. Here, we propose that phosphorylated tau protein could be playing the role of potential connector and, therefore, that a combined therapy involving antioxidants and check points for synaptic plasticity during early stages of the disease could become a viable therapeutic option for AD treatment.

Publication types

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

MeSH terms

  • Alzheimer Disease / metabolism*
  • Humans
  • Mitochondria / metabolism*
  • Oxidative Stress / physiology
  • tau Proteins / metabolism*


  • tau Proteins