Cloning and sequencing of the cDNA encoding an isoform of microtubule‐associated protein tau containing four tandem repeats: differential expression of tau protein mRNAs in human brain.
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We have isolated cDNA clones encoding a 383-amino acid isoform of the human microtubule-associated protein tau. It differs from previously determined tau sequences by the presence of an additional repeat of 31 amino acids, giving four, rather than three, tandem repeats in its carboxy-terminal half. The extra repeat is encoded by a separate exon. Probes derived from cDNA clones encoding the three (type I) and four repeat (type II) tau protein isoforms detected mRNAs for both forms in all adult human brain areas examined. However, in foetal brain only type I mRNA was found. Type I and type II mRNAs were present in pyramidal cells in cerebral cortex. In the hippocampal formation, type I mRNA was found in pyramidal and granule cells; type II mRNA was detected in most, though not all, pyramidal cells but not in granule cells. These observations indicate that tau protein mRNAs are expressed in a stage- and cell-specific manner. Tau protein is found in the protease-resistant core of the paired helical filament, the major constituent of the neurofibrillary tangle in Alzheimer's disease. Taken in conjunction with previous findings, the present results indicate that both the three and four repeat-containing tau protein isoforms are present in the core of the paired helical filament.
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Alternative splice variation including exons 2, 3, and 10 generates up to six differing tau isoform variants in the human brain.
“Alternative splice variation including exons 2, 3, and 10 generates up to six differing tau isoform variants in the human brain [106, 107].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [107]
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The toxicity of tau in Alzheimer disease: turnover, targets and potential therapeutics
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Beaudet, D., Berger, C. L., & Hendricks, A. G. (2026) · eLife · doi:10.7554/elife.110011
- Authors
- Goedert, M., Spillantini, M. G., Potier, M. C., Ulrich, J., & Crowther, R. A.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Venue
- The EMBO Journal
- Published
- 1989-02-01
- Volume
- 8
- Issue
- 2
- Pages
- 393-399
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC400819
- OpenAlex
- W150987474
- Cited by
- 1,037
- References
- 30
- Citations by year
- 2026: 13 · 2025: 29 · 2024: 23 · 2023: 31 · 2022: 22 · 2021: 43 · 2020: 37 · 2019: 33 · 2018: 41 · 2017: 28 · 2016: 27 · 2015: 40 · 2014: 33 · 2013: 23 · 2012: 27
- FWCI
- 20.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- tau protein, microtubule-associated proteins, tau isoforms, tandem repeats, cDNA cloning, differential gene expression, human brain, fetal brain, hippocampus, cerebral cortex, pyramidal neurons, granule cells, neurofibrillary tangles, Alzheimer's disease
- MeSH terms
- Amino Acid Sequence, Base Sequence, Brain, Cloning, Molecular, DNA, Gene Expression Regulation, Humans, Microtubule-Associated Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Repetitive Sequences, Nucleic Acid, RNA, Messenger, Tissue Distribution, tau Proteins
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