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

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posted on 2023-06-09, 19:49 authored by Youssra Al-Hilaly, Bronwen E Foster, Luca Biasetti, Liisa Lutter, Saskia Pollack, Janet E Rickard, John M D Storey, Charles R Harrington, Wei-Feng Xue, Claude M Wischik, Louise SerpellLouise Serpell
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-ß-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.

History

Publication status

  • Published

File Version

  • Published version

Journal

FEBS Letters

ISSN

0014-5793

Publisher

Wiley

Page range

1-7

Department affiliated with

  • Neuroscience Publications

Research groups affiliated with

  • Dementia Research Group Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2019-12-03

First Open Access (FOA) Date

2019-12-03

First Compliant Deposit (FCD) Date

2019-12-03

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