Journal
FEBS LETTERS
Volume 594, Issue 5, Pages 944-950Publisher
WILEY
DOI: 10.1002/1873-3468.13675
Keywords
Alzheimer's disease; neurofibrillary tangles; paired helical filaments; tau
Funding
- Biochemical society
- Mustansiriyah University, Baghdad, Iraq
- BBSRC [BB/S003312/1]
- EPSRC [EP/R513246/1]
- BBSRC [BB/S003657/1, BB/S003312/1] Funding Source: UKRI
- EPSRC [2119785] Funding Source: UKRI
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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-beta-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.
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