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.
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Authors | J 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 |
Journal | Brain 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 |
PMID | 15950767
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Protein Isoforms
- RNA Splice Sites
- RNA, Messenger
- tau Proteins
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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)
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