HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Quantitative analysis of tau isoform transcripts in sporadic tauopathies.

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.
AuthorsJ W Connell, T Rodriguez-Martin, G M Gibb, N M Kahn, A J Grierson, D P Hanger, T Revesz, P L Lantos, B H Anderton, J-M Gallo
JournalBrain research. Molecular brain research (Brain Res Mol Brain Res) Vol. 137 Issue 1-2 Pg. 104-9 (Jun 13 2005) ISSN: 0169-328X [Print] Netherlands
PMID15950767 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Protein Isoforms
  • RNA Splice Sites
  • RNA, Messenger
  • tau Proteins
Topics
  • Aged
  • Alternative Splicing (genetics)
  • Alzheimer Disease (genetics, metabolism, physiopathology)
  • Base Sequence (genetics)
  • Brain (metabolism, pathology, physiopathology)
  • Dementia (genetics, metabolism, physiopathology)
  • Exons (genetics)
  • Humans
  • Middle Aged
  • Molecular Sequence Data
  • Mutation (genetics)
  • Pick Disease of the Brain (genetics, metabolism, physiopathology)
  • Polymorphism, Genetic (genetics)
  • Protein Isoforms (genetics, metabolism)
  • Protein Processing, Post-Translational (genetics)
  • RNA Splice Sites (genetics)
  • RNA, Messenger (analysis, genetics)
  • Reverse Transcriptase Polymerase Chain Reaction (methods)
  • Tauopathies (genetics, metabolism, physiopathology)
  • tau Proteins (genetics, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: