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Twelve phosphomimetic mutations induce the assembly of recombinant full-length human tau into paired helical filaments.

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Paper

Loaded from Europe PMC by your browser, not stored by OSCR: doi.org · Europe PMC

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The authors' code

Python · 62 lines · 1.5 KB · CC-BY-4.0

  1. import os
  2. import os.path as op
  3. from ij import IJ
  4. from ij import WindowManager as wm
  5. import time
  7. save_path = "/Users/user123/Experiments/Exp001/Images"
  8. image_path = save_path
  10. def analysis(save_path, image_path):
  11. List_of_images = []
  12. if image_path == 'NA':
  13. List_of_images = wm.getImageTitles()
  14. else:
  15. try:
  16. for roots, dirs, files in os.walk(image_path):
  17. for f in files:
  18. if f.endswith('.tif'):
  19. im = IJ.openImage(op.join(roots, f))
  20. im.show()
  21. except:
  22. return
  23. List_of_images = wm.getImageTitles()
  24. IJ.run("Clear Results")
  25. for tit in List_of_images:
  26. imp = wm.getImage(tit)
  27. wm.setCurrentWindow(imp.getWindow())
  28. try:
  29. IJ.redirectErrorMessages()
  30. IJ.runMacro('''
  31. run("Focus Search Bar");
  32. run("Subtract Background...", "rolling=5 sliding");
  33. run("Focus Search Bar");
  34. run("Median...", "radius=10");
  35. run("Focus Search Bar");
  36. run("Unsharp Mask...", "radius=5 mask=0.90");
  37. run("Focus Search Bar");
  38. setAutoThreshold("Default dark");
  39. setOption("BlackBackground", true);
  40. run("Convert to Mask");
  41. run("Focus Search Bar");
  42. run("Set Measurements...", "area limit redirect=None decimal=3");
  43. run("Focus Search Bar");
  44. run("Analyze Particles...", "size=25-Infinity pixel display exclude summarize");
  45. ''')
  46. except:
  47. continue
  48. imp.changes = False
  49. imp.close()
  51. IJ.selectWindow("Summary")
  52. result_path = op.join(save_path, "DAPI_summary.csv")
  53. IJ.saveAs("text", result_path)
  55. if __name__ in ["__main__", "__builtin__"]:
  56. if image_path == "":
  57. image_path = 'NA'
  58. analysis(save_path,image_path)

batch_macro_nuclear counting.py, under CC-BY-4.0 · at the source

Overview

Authors: Sofia Lövestam1, Jane L Wagstaff1, Taxiarchis Katsinelos1, Jenny Shi1, Stefan MV Freund1, Michel Goedert1, Sjors HW Scheres1
ORCID iDs: Sofia Lövestam, Michel Goedert, Sjors HW Scheres
  1. MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
Institutions: MRC Laboratory of Molecular Biology (United Kingdom)
Journal: eLife, volume 14, article RP104778
Dates: published online 20 May 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.7554/elife.104778 · PMID 42159330 · PMCID PMC13189620 · OpenAlex W4406456488
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: histology / microscopy (modality), human (organism), Alzheimer's / dementia (population), cellular / molecular (subfield)
Methods: Machine learning, fMRI & imaging
Keywords: Human
MeSH: Mutation*, tau Proteins*, Cryoelectron Microscopy, Humans, Phosphorylation, Recombinant Proteins (* major topic)
Topic: Prion Diseases and Protein Misfolding (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Medical Research Council (MC_UP_A025-1013, MC_U105184291)
Citations: cited by 6 papers (Europe PMC); 58 references in the paper
Research resources: RRID:AB_10064068, RRID:AB_2535804, RRID:Addgene_12259, RRID:Addgene_12260, RRID:Addgene_79121, HEK293T cells were purchased from ATCC RRID:CVCL_0063

Abstract

The assembly of tau into amyloid filaments is associated with more than 20 neurodegenerative diseases, collectively termed tauopathies. Electron cryo-microscopy (cryo-EM) structures of brain-derived tau filaments revealed that specific structures define different diseases, triggering a quest for the development of experimental model systems that replicate the structures of disease. Here, we describe 12 phosphomimetic serine/threonine-to-aspartate mutations in tau, which we term PAD12, that collectively induce the in vitro assembly of full-length three-repeat tau into filaments with the same structure as paired helical filaments extracted from the brains of individuals with Alzheimer’s disease. Solution-state nuclear magnetic resonance spectroscopy suggests that phosphomimetic mutations in the carboxy-terminal domain of tau may facilitate filament formation by disrupting an intramolecular interaction between two IVYK motifs. PAD12 tau can be used for both nucleation-dependent and multiple rounds of seeded assembly in vitro, as well as for the seeding of tau biosensor cells. PAD12 tau can be assembled into paired helical filaments under various shaking conditions, with the resulting filaments being stable for extended periods of time. They can be labelled with fluorophores and biotin. Tau filaments extracted from the brains of individuals with Alzheimer’s disease have been known to be made of hyperphosphorylated and abnormally phosphorylated full-length tau, but it was not known if the presence of this post-translational modification is more than a mere correlation. Our findings suggest that hyperphosphorylation of tau may be sufficient for the formation of the Alzheimer tau fold. PAD12 tau will be a useful tool for the study of molecular mechanisms of neurodegeneration.

Reproduced under the paper's license (CC BY), from the paper cited above.

Repositories

Its files are read in the Code ↔ Paper reader above.

Zenodo 18236965

License: CC-BY-4.0
State: the link answers, verified on 28 September 2026
Evidence: files inventoried
Size: 1 file
Software Heritage: not checked
Found in: “Data availability”
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Tools: ImageJ / Fiji (1 file)
Availability: 1 check, the latest on 28 September 2026: the link answers (HTTP 200)
  • 28 September 2026: the link answers (HTTP 200)
2 files
At the source: doi.org/10.5281/zenodo.18236965

Zenodo 18236945

License: CC-BY-4.0
State: the link answers, verified on 28 September 2026
Evidence: files inventoried
Size: 1 file
Software Heritage: not checked
Found in: “Data availability”
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Tools: ImageJ / Fiji (1 file)
Availability: 1 check, the latest on 28 September 2026: the link answers (HTTP 200)
  • 28 September 2026: the link answers (HTTP 200)
2 files
At the source: doi.org/10.5281/zenodo.18236945

tkatsine/counting-protein-aggregates

License: none: the authors keep all their rights
State: the link answers, verified on 28 September 2026
Evidence: files inventoried
Commit: 3a8a90ee1e7eba07db46327de55cdadb16dd2c61, 12 June 2025
Languages: Python (1)
Size: 2 files, 1 script
Software Heritage: not archived
Found in: the Zenodo archive record
Holds: README
Not found: license file, CITATION.cff, environment file, tests, continuous integration, documentation
Tools: ImageJ / Fiji (1 file)
Availability: 1 check, the latest on 28 September 2026: the link answers
  • 28 September 2026: the link answers
2 files
At the source: github.com/tkatsine/Counting-protein-aggregates/tree/Counting_protein_aggregates

tkatsine/nuclear-counting

License: none: the authors keep all their rights
State: the link answers, verified on 28 September 2026
Evidence: files inventoried
Commit: 2d845dff6104d5bcf1c0cc19fb25c6ef222745ba, 12 June 2025
Languages: Python (1)
Size: 2 files, 1 script
Software Heritage: not archived
Found in: the Zenodo archive record
Holds: README
Not found: license file, CITATION.cff, environment file, tests, continuous integration, documentation
Tools: ImageJ / Fiji (1 file)
Availability: 1 check, the latest on 28 September 2026: the link answers
  • 28 September 2026: the link answers
2 files
At the source: github.com/tkatsine/Nuclear-counting/tree/Nuclear_counting

The paper's code and data availability statement is in the Data section.

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

  • 4 repositories of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 4 scripts, each with its path and the digest of its content;
  • no match between paragraphs and code yet;
  • neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

No dataset and no data link were found in the paper.

Data availability

PAD12 constructs and tau reporter cells fare available upon request. Cryo-EM maps and atomic models for PHFs formed with a mixture of 0N3R:0N4R PAD12 tau and for PHFs formed with 0N3R PAD12 tau and seeded with filaments extracted from the brain of an individual with AD have been deposited in EMDB and the PDB (see Table 2). NMR data (HSQC spectra plus our assignments) have been deposited to the BMRB (accession codes: 52694 – tau297–441 wt; 52695 – tau297–441 PAD-12; 52696 – tau151–391 wt; 52697 – tau151–391 PAD-12; and 53230 – tau297–441 Δ392–395). Scripts for counting of nuclei and protein aggregates are available from Zenodo, under DOIs 10.5281/zenodo.18236965 (https://doi.org/10.5281/zenodo.18236965) and 10.5281/zenodo.18236945 (https://doi.org/10.5281/zenodo.18236945), respectively.

The following datasets were generated:

Lovestam S, Scheres SHW, Goedert M. 2024. PAD12 0N3R:0N4R tau PHF. Worldwide Protein Data Bank.

Lovestam S, Scheres SHW, Goedert M. 2024. PAD12 0N3R tau PHF seeded by AD. Worldwide Protein Data Bank.

Lovestam S, Scheres SHW, Goedert M. 2024. 297-441 delta392-395 tau filaments. Worldwide Protein Data Bank.

Lovestam S, Wagstaff J, Freund S, Scheres S. 2026. Tau297-441 wt. Biological Magnetic Resonance Data Bank.

Lovestam S, Wagstaff J, Freund S, Scheres S. 2026. Tau297-441 PAD12. Biological Magnetic Resonance Data Bank.

Lovestam S, Wagstaff J, Freund S, Scheres S. 2026. Tau 151-391 WT. Biological Magnetic Resonance Data Bank.

Lovestam S, Wagstaff J, Freund S, Scheres S. 2026. Tau151-391 PAD12. Biological Magnetic Resonance Data Bank.

Lovestam S, Wagstaff J, Freund S, Scheres S. 2026. Tau297-441 delta. Biological Magnetic Resonance Data Bank.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 7 authors, 1 keyword, 6 MeSH terms, 1 funder, 58 references, 6 RRIDs.

Cite

This paper

Lövestam, S., Wagstaff, J. L., Katsinelos, T., Shi, J., Freund, S. M., Goedert, M., & Scheres, S. H. (2026). Twelve phosphomimetic mutations induce the assembly of recombinant full-length human tau into paired helical filaments. eLife, 14, RP104778. https://doi.org/10.7554/elife.104778

BibTeX

@article{lovestam2026twelve,
author = {Lövestam, Sofia and Wagstaff, Jane L and Katsinelos, Taxiarchis and Shi, Jenny and Freund, Stefan MV and Goedert, Michel and Scheres, Sjors HW},
title = {{Twelve phosphomimetic mutations induce the assembly of recombinant full-length human tau into paired helical filaments}},
journal = {eLife},
year = {2026},
month = may,
volume = {14},
pages = {RP104778},
publisher = {eLife Sciences Publications, Ltd},
issn = {2050-084X},
doi = {10.7554/elife.104778},
url = {https://doi.org/10.7554/elife.104778},
pmid = {42159330},
pmcid = {PMC13189620}
}

RIS

TY - JOUR
AU - Lövestam, Sofia
AU - Wagstaff, Jane L
AU - Katsinelos, Taxiarchis
AU - Shi, Jenny
AU - Freund, Stefan MV
AU - Goedert, Michel
AU - Scheres, Sjors HW
TI - Twelve phosphomimetic mutations induce the assembly of recombinant full-length human tau into paired helical filaments
T2 - eLife
J2 - Elife
PY - 2026
DA - 2026/05/20
VL - 14
SP - RP104778
SN - 2050-084X
PB - eLife Sciences Publications, Ltd
DO - 10.7554/elife.104778
UR - https://doi.org/10.7554/elife.104778
LA - en
ER -

CSL-JSON

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"type": "article-journal",
"title": "Twelve phosphomimetic mutations induce the assembly of recombinant full-length human tau into paired helical filaments",
"container-title": "eLife",
"author": [
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"family": "Lövestam",
"given": "Sofia"
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{
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{
"family": "Shi",
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{
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{
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{
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"given": "Sjors HW"
}
],
"container-title-short": "Elife",
"volume": "14",
"page": "RP104778",
"DOI": "10.7554/elife.104778",
"PMID": "42159330",
"PMCID": "PMC13189620",
"ISSN": "2050-084X",
"publisher": "eLife Sciences Publications, Ltd",
"URL": "https://doi.org/10.7554/elife.104778",
"language": "en",
"issued": {
"date-parts": [
[
2026,
5,
20
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]
}
}

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