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

Journal Article · Wed Jun 01 00:00:00 EDT 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.11.4051· OSTI ID:5565392

Goedert, M; Wischik, C M; Crowther, R A; Walker, J E; Klug, A ^[1]

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1. Medical Research Council Laboratory of Molecular Biology, Cambridge (England)

Screening of cDNA libraries prepared from the frontal cortex of an Alzheimer's 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's 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 long, with a wide distribution in normal human brain. Tau protein mRNAs were found in normal amounts in the frontal cortex from patients with Alzheimer's 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's disease.

• OSTI ID: 5565392
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 85:11; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACID SEQUENCE
ANIMALS
BIOLOGICAL EVOLUTION
BODY
BRAIN
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM
DISEASES
DNA
DNA SEQUENCING
MAMMALS
MESSENGER-RNA
MICE
MICROTUBULES
MOLECULAR STRUCTURE
NERVOUS SYSTEM
NERVOUS SYSTEM DISEASES
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PATIENTS
PROTEINS
RECOMBINANT DNA
RNA
RODENTS
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES