Tau (297-391) forms filaments that structurally mimic the core of paired helical filaments in Alzheimer's disease brain

Youssra K Al-Hilaly* (Corresponding Author), Bronwen E Foster, Luca Biasetti, Liisa Lutter, Saskia J Pollack, Janet E Rickard, John M D Storey, Charles R Harrington, Wei-Feng Xue, Claude M Wischik, Louise C Serpell

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)
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Abstract

The constituent paired helical filaments (PHFs) in neurofibrillary tangles are insoluble intracellular deposits central to the development of Alzheimer's disease (AD) and other tauopathies. Full-length tau requires the addition of anionic cofactors such as heparin to enhance assembly. We have shown that a fragment from the proteolytically stable core of the PHF, tau 297-391 known as 'dGAE', spontaneously forms cross-β-containing PHFs and straight filaments under physiological conditions. Here, we have analysed and compared the structures of the filaments formed by dGAE in vitro with those deposited in the brains of individuals diagnosed with AD. We show that dGAE forms PHFs that share a macromolecular structure similar to those found in brain tissue. Thus, dGAEs may serve as a model system for studying core domain assembly and for screening for inhibitors of tau aggregation.

Original languageEnglish
Pages (from-to)944-950
Number of pages7
JournalFEBS LETTERS
Volume594
Issue number5
Early online date1 Dec 2019
DOIs
Publication statusPublished - Mar 2020

Keywords

  • Alzheimer’s disease
  • neurofibrillary tangles
  • paired helical filaments
  • tau

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