Tau (297‐391) forms filaments that structurally mimic the core of paired helical filaments in Alzheimer's disease brain. Issue 5 (1st December 2019)

• Record Type: Journal Article
• Authors: 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.; Serpell, Louise C.
• Is Part Of: FEBS letters. Volume 594:Issue 5(2020)
• Page Start: 944
• Page End: 950
• Publication Date: 2019-12-01
• Subjects: Alzheimer's disease -- neurofibrillary tangles -- paired helical filaments -- tau; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.13675
• Languages: English
• ISSNs: 0014-5793

Abstract

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. Abstract : Truncated tau (297‐391) is the principal component of the core of paired helical filaments (PHFs) in neurofibrillary tangles isolated from Alzheimer's brain tissue. Truncated tau forms filaments in vitro that share macromolecular characteristics with PHFs found in vivo . Truncated tau, without modification, is sufficient for the assembly of PHFs.