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

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

FEBS letters (2019-11-14)
Youssra K Al-Hilaly, 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
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Tau (T22), oligomeric Antibody, serum, from rabbit
Sigma-Aldrich
Anti-TAU antibody produced in rabbit, affinity isolated antibody