Quantitative analysis of tau isoform transcripts in sporadic tauopathies

Brain Res Mol Brain Res. 2005 Jun 13;137(1-2):104-9. doi: 10.1016/j.molbrainres.2005.02.014. Epub 2005 Mar 29.


A number of neurodegenerative diseases, including Alzheimer's disease (AD), are characterized by intraneuronal accumulation of the tau protein. Some forms of FTDP-17 are caused by mutations in the tau gene affecting exon 10 splicing. Therefore, dysregulation of tau pre-mRNA splicing may be a contributing factor to sporadic tauopathies. To address this question, we devised a real-time RT-PCR strategy based on the use of a single fluorogenic probe to evaluate the ratio between tau isoforms containing or lacking exon 10 (4R/3R ratio) in post-mortem brain samples. We found a two- to six-fold increase in the 4R/3R ratio in cases of FTDP-17 linked to a splice site mutation, hence confirming the validity of the strategy. The difference in the 4R/3R ratio in the superior temporal and superior frontal gyri between AD and control brains was not statistically significant. Similarly, there was no significant difference in the 4R/3R ratio between Pick's disease cases and controls, indicating that the predominance of tau3R protein in PiD reflects post-translational modifications of specific isoforms. This study indicates that post-translational events are likely to be the main factors controlling tau isoform composition in sporadic tauopathies and highlights the benefit of quantitative RT-PCR in the assessment of splicing abnormalities in tauopathies.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alternative Splicing / genetics*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology
  • Base Sequence / genetics
  • Brain / metabolism*
  • Brain / pathology
  • Brain / physiopathology
  • Dementia / genetics
  • Dementia / metabolism
  • Dementia / physiopathology
  • Exons / genetics
  • Humans
  • Middle Aged
  • Molecular Sequence Data
  • Mutation / genetics*
  • Pick Disease of the Brain / genetics
  • Pick Disease of the Brain / metabolism
  • Pick Disease of the Brain / physiopathology
  • Polymorphism, Genetic / genetics*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Processing, Post-Translational / genetics
  • RNA Splice Sites / genetics
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Tauopathies / genetics*
  • Tauopathies / metabolism
  • Tauopathies / physiopathology
  • tau Proteins / genetics*
  • tau Proteins / metabolism


  • Protein Isoforms
  • RNA Splice Sites
  • RNA, Messenger
  • tau Proteins