Quantitative analysis of tau isoform transcripts in sporadic tauopathies

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Abstract

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.
Original languageEnglish
Pages (from-to)104 - 109
Number of pages6
JournalMolecular Brain Research
Volume137
Issue number1-2
DOIs
Publication statusPublished - 13 Jun 2005

Keywords

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

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