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Cited by 1,134Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Cloning and sequencing of the cDNA encoding a core protein of the paired helical filament of Alzheimer disease: identification as the microtubule-associated protein tau

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Goedert, M, Wischik, C M, Crowther, R A, Walker, J E, Klug, A·1988·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.85.11.4051PMC PMC280359
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Abstract

Screening of cDNA libraries prepared from the frontal cortex of an Alzheimer disease patient and from fetal human brain has led to isolation of the cDNA for a core protein of the paired helical filament of Alzheimer disease. The partial amino acid sequence of this core protein was used to design synthetic oligonucleotide probes. The cDNA encodes a protein of 352 amino acids that contains a characteristic amino acid repeat in its carboxyl-terminal half. This protein is highly homologous to the sequence of the mouse microtubule-associated protein tau and thus constitutes the human equivalent of mouse tau. RNA blot analysis indicates the presence of two major transcripts, 6 and 2 kilobases lon g, with a wide distribution in normal human brain. Tau protein mRNAs were found in normal amounts in the frontal cortex from patients with Alzheimer disease. The proof that at least part of tau protein forms a component of the paired helical filament core opens the way to understanding the mode of formation of paired helical filaments and thus, ultimately, the pathogenesis of Alzheimer disease.

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  • There are six tau isoforms expressed in the mature human brain.

    “There are six tau isoforms expressed in the mature human brain”

    From Tau hyperphosphorylation impairs cooperative binding to microtubules and perturbs organelle trafficking in neurons (2026) · cites this paper as Goedert et al., 1988

    The Discussion (page not provided) reports one sequenced form of human tau and describes cDNA evidence for a second form, suggesting that human tau mRNA may be alternatively spliced. It does not establish six isoforms or specify their expression in the mature human brain; its 6-kb measurement refers to transcript length, not isoform count. (LLM, conf=0.85)

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Research works printed but not linked: 16

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  12. [25]Huynh, T. V., Young, R. A. & Davis, R. W. (1985) in DNA Cloning—A Practical Approach, ed. Glover, D. M. (IRL, Oxford), Vol. 1, pp. 49–78.
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Cited by

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Authors
Goedert, M., Wischik, C. M., Crowther, R. A., Walker, J. E., & Klug, A.
Affiliations
MRC Laboratory of Molecular Biology (GB)
ORCID
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
1988-06
Volume
85
Issue
11
Pages
4051-4055
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.85.11.4051
PMC
PMC280359
OpenAlex
W2141839336
Cited by
1,134
References
3
Citations by year
2026: 21 · 2025: 28 · 2024: 52 · 2023: 33 · 2022: 44 · 2021: 50 · 2020: 53 · 2019: 49 · 2018: 33 · 2017: 44 · 2016: 37 · 2015: 40 · 2014: 30 · 2013: 32 · 2012: 34
FWCI
32.13
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
tau protein, Alzheimer's disease, microtubule-associated proteins, cDNA cloning, frontal cortex, mRNA transcripts, protein homology, neurofibrillary tangles, pathogenesis
MeSH terms
Alzheimer Disease, Amino Acid Sequence, Base Sequence, Brain, Cloning, Molecular, DNA, Humans, Microtubule-Associated Proteins, Molecular Sequence Data, RNA, Messenger, Tissue Distribution, tau Proteins

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