Reduction of acetylated alpha-tubulin immunoreactivity in neurofibrillary tangle-bearing neurons in Alzheimer's disease

J Neuropathol Exp Neurol. 1996 Sep;55(9):964-72. doi: 10.1097/00005072-199609000-00003.


A disturbance of the microtubule network in neurons containing neurofibrillary tangles (NFT), one of the characteristic neuropathological lesions in Alzheimer's disease, has been advocated as a central physiopathological mechanism leading to neuronal dysfunction in NFT-containing neurons. The accumulation of "paired helical filament-tau," the main proteineous component of NFT, in affected neurons has been proposed to induce a decrease of microtubule stability in these cells. To further explore the hypothesis of a decrease in microtubule stability in Alzheimer's disease, we have investigated in this study the relative content in stable microtubules in neurons with different amount of NFT. We used a double immunocytochemical labeling technique with antibodies to tau (as a marker of NFT) and to acetylated alpha-tubulin (as a marker of stable microtubules) and rated on a semi-quantitative scale the tau and acetylated alpha-tubulin-immunoreactivities in the same neurons. We observed a strong reduction in acetylated alpha-tubulin immunoreactivity in most NFT-bearing neurons; a statistical relationship between tau and acetylated alpha-tubulin immunoreactivity was demonstrated, assuming an inverse relationship between the presence of tau-immunoreactive NFT and tubulin-immunoreactivity in neurons. This reduction was already seen in the neuronal population with a relatively lower tau-immunoreactivity, suggesting that reduction in acetylated alpha-tubulin immunoreactivity, and reduction in microtubule stability, could be an early event in these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism*
  • Antibody Specificity
  • Cell Count
  • Data Interpretation, Statistical
  • Hippocampus / cytology
  • Humans
  • Immunohistochemistry
  • Microtubules / chemistry
  • Neurofibrillary Tangles / chemistry*
  • Neurons / chemistry*
  • Neurons / cytology
  • Pyramidal Cells / chemistry
  • Pyramidal Cells / cytology
  • Tubulin / analysis
  • Tubulin / immunology*
  • Tubulin / metabolism
  • tau Proteins / analysis
  • tau Proteins / immunology
  • tau Proteins / metabolism


  • Tubulin
  • tau Proteins