Solid-state NMR of paired helical filaments formed by the core tau fragment tau(297-391)

Youssra K. Al-Hilaly, Connor Hurt, Janet E. Rickard, Charles R. Harrington, John M.D. Storey, Claude M. Wischik, Louise C. Serpell, Ansgar B. Siemer* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Aggregation of the tau protein into fibrillar cross-β aggregates is a hallmark of Alzheimer’s diseases (AD) and many other neurodegenerative tauopathies. Recently, several core structures of patient-derived tau paired helical filaments (PHFs) have been solved revealing a structural variability that often correlates with a specific tauopathy. To further characterize the dynamics of these fibril cores, to screen for strain-specific small molecules as potential biomarkers and therapeutics, and to develop strain-specific antibodies, recombinant in-vitro models of tau filaments are needed. We recently showed that a 95-residue fragment of tau (from residue 297 to 391), termed dGAE, forms filaments in vitro in the absence of polyanionic co-factors often used for in vitro aggregation of full-length tau. Tau(297-391) was identified as the proteolytic resistant core of tau PHFs and overlaps with the structures characterized by cryo-electron microscopy in ex vivo PHFs, making it a promising model for the study of AD tau filaments in vitro. In the present study, we used solid-state NMR to characterize tau(297-391) filaments and show that such filaments assembled under non-reducing conditions are more dynamic and less ordered than those made in the presence of the reducing agent DTT. We further report the resonance assignment of tau(297-391)+DTT filaments and compare it to existing core structures of tau.

Original languageEnglish
Article number988074
Number of pages12
JournalFrontiers in Neuroscience
Early online date8 Dec 2022
Publication statusPublished - 8 Dec 2022

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health under grant numbers (R01AG061865 and R01NS120704). YA-H was supported by WisTa Laboratories Ltd.

Data Availability Statement

The Supplementary Material for this article can be found online at:

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below:, BMRB ID 51483.


  • Alzheimer’s disease
  • amyloid structure
  • neurodegenerative diseases
  • solid-state NMR
  • tau protein


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