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

Al‐Hilaly, Youssra K, Foster, Bronwen E, Biasetti, Luca, Lutter, Liisa, Pollack, Saskia J, Rickard, Janet E, Storey, John M D, Harrington, Charles R, Xue, Wei‐Feng, Wischik, Claude M and Serpell, Louise C (2019) Tau (297‐391) forms filaments that structurally mimic the core of paired helical filaments in Alzheimer’s disease brain. FEBS Letters. pp. 1-7. ISSN 0014-5793

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Neuroscience
Research Centres and Groups: Dementia Research Group
Subjects: R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry
Depositing User: Youssra Al-Hilaly
Date Deposited: 03 Dec 2019 08:48
Last Modified: 03 Dec 2019 09:00
URI: http://sro.sussex.ac.uk/id/eprint/88374

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