PMID: 2504257Jan 1, 1989Paper

The repeat region of microtubule-associated protein tau forms part of the core of the paired helical filament of Alzheimer's disease

Annals of Medicine
T CrowtherC M Wischik

Abstract

The paired helical filament, the principal component of the neurofibrillary tangles characteristic of Alzheimer's disease, is shown to consist of two structurally distinct parts. An external fuzzy region can be removed by pronase treatment to leave a pronase-resistant morphologically recognizable core. A monoclonal antibody has been raised which both decorates the core and labels peptide fragments extracted from the core. Amino acid sequence derived from such peptides was used to design oligonucleotide probes with which cDNA libraries were screened and clones coding for the corresponding proteins were isolated. The sequences proved to code for two isoforms of human microtubule-associated protein tau, which contained respectively three or four tandem repeats of 31 or 32 amino acids each with a characteristic Pro-Gly-Gly-Gly motif. The patterns of mRNA expression for the two isoforms were found to be stage and cell-type specific but were apparently unaltered in Alzheimer's disease. The repeat region of tau is believed to be the microtubule binding domain and it is this region of the molecule which is tightly and specifically bound in the core of the paired helical filament.

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Citations

Dec 9, 1997·Neurobiology of Aging·J SongP D Coleman
Sep 25, 2012·Journal of the American Chemical Society·Shana Elbaum-Garfinkle, Elizabeth Rhoades
Jul 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·M NovakC M Wischik
Aug 23, 2007·BMC Cell Biology·Alphan AltinokKenneth Rose
May 27, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Elisa A Waxman, Benoit I Giasson
Apr 16, 2014·Proceedings of the National Academy of Sciences of the United States of America·Shana Elbaum-GarfinkleElizabeth Rhoades
Apr 29, 2015·Proceedings of the National Academy of Sciences of the United States of America·Yann FichouMartin Weik
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Aug 17, 2005·Microscopy Research and Technique·Hanna Ksiezak-Reding, Joseph S Wall
Aug 9, 2017·Proceedings of the National Academy of Sciences of the United States of America·Clément DespresCaroline Smet-Nocca
Feb 15, 2018·Frontiers in Neuroscience·Fuyuki Kametani, Masato Hasegawa
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Jun 19, 2008·Biochemistry·Dylan W PetersonJohn Lew
Mar 27, 2021·The Biochemical Journal·Wei Siang LeeLars M Ittner
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Feb 18, 2020·Biochimica Et Biophysica Acta. Biomembranes·Mehdi AzouzAlexandre Ciaccafava

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