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Correlative ultrastructural mapping of Lewy pathology reveals regional diversity in Parkinson's and dementia with Lewy bodies.

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Paper

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The authors' code

Jupyter notebook · 58 lines · 1.8 KB · GPL-3.0

  1. # %%
  2. import cv2
  3. import numpy as np
  4. import os
  5. import tifffile
  7. def crop_masked_regions(image_path, mask_path, output_dir, padding=10):
  8. # Read the image and mask
  9. image = cv2.imread(image_path)
  10. mask = tifffile.imread(mask_path) # Use tifffile to read the mask
  12. # Convert mask to 32-bit float if it's not already
  13. if mask.dtype != np.float32:
  14. mask = mask.astype(np.float32)
  16. # Prepare mask for contour finding
  17. mask_for_contours = (mask > 0).astype(np.uint8) * 255
  19. # Find contours in the mask
  20. contours, _ = cv2.findContours(mask_for_contours, cv2.RETR_EXTERNAL, cv2.CHAIN_APPROX_SIMPLE)
  22. # Create output directories
  23. crops_dir = os.path.join(output_dir, 'crops')
  24. masks_dir = os.path.join(output_dir, 'masks')
  25. os.makedirs(crops_dir, exist_ok=True)
  26. os.makedirs(masks_dir, exist_ok=True)
  28. # Process each contour
  29. for i, contour in enumerate(contours):
  30. # Get bounding box
  31. x, y, w, h = cv2.boundingRect(contour)
  33. # Add padding
  34. x_start = max(0, x - padding)
  35. y_start = max(0, y - padding)
  36. x_end = min(image.shape[1], x + w + padding)
  37. y_end = min(image.shape[0], y + h + padding)
  39. # Crop image and mask
  40. crop = image[y_start:y_end, x_start:x_end]
  41. crop_mask = mask[y_start:y_end, x_start:x_end]
  43. # Save cropped image
  44. cv2.imwrite(os.path.join(crops_dir, f'{i}.tif'), crop)
  46. # Save mask as 32-bit float TIFF using tifffile without compression
  47. tifffile.imwrite(os.path.join(masks_dir, f'{i}.tif'), crop_mask)
  49. print(f"Processed {len(contours)} regions. Crops saved in {crops_dir}, masks saved in {masks_dir}")
  51. # Example usage
  52. image_path = ''
  53. mask_path = ''
  54. output_dir = ''
  55. crop_masked_regions(image_path, mask_path, output_dir)
  57. # %% [markdown]

crop_mitochondria.ipynb at commit 093440c, under GPL-3.0 · at the source

Overview

Authors: Notash Shafiei1,2, Daria Proniakova1, Marija Simjanoska1, Anniken Mathea Rafnum Sjødal1, Daniel Stähli1,2, Lukas van den Heuvel1,2, Marta Di Fabrizio1,2, Eve Aaron1, Sandor Kasas1, Mathis Solal Krause1,3, Mallory Wittwer3, Julika Radecke1,2, Henning Stahlberg1,2, Wilma D. J. van de Berg4,5, Amanda J. Lewis1,2
ORCID iDs: Notash Shafiei, Eve Aaron, Henning Stahlberg
  1. Laboratory of Biological Electron Microscopy, Institute of Physics, School of Basic Sciences, École Polytechnique Fédérale de Lausanne,Rt. de la Sorge, 1015 Lausanne, Switzerland
  2. Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne,Rt. de la Sorge, 1015 Lausanne, Switzerland
  3. Center for Imaging, École Polytechnique Fédérale de Lausanne,Station 11, 1015 Lausanne, Switzerland
  4. Department of Anatomy and Neurosciences, Section Clinical Neuroanatomy and Biobanking, Amsterdam Neuroscience, Amsterdam University Medical Centre, Vrije University Amsterdam,O|2 Life Sciences building, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands
  5. Amsterdam Neuroscience, Program Neurodegeneration, Amsterdam University Medical Centre,Amsterdam, The Netherlands
Institutions: École Polytechnique Fédérale de Lausanne (Switzerland); University of Lausanne (Switzerland); Amsterdam Neuroscience (Netherlands)
Journal: Acta neuropathologica, volume 152, issue 1, article 5
Dates: received 19 December 2025; accepted 5 June 2026; published online 8 July 2026; in print 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1007/s00401-026-03039-w · PMID 42420695 · PMCID PMC13346217 · OpenAlex W7167701393
Open access: hybrid, a free copy (OpenAlex)
Status: code verified
Categories: histology / microscopy (modality), human (organism), Alzheimer's / dementia (population), Parkinson's (population), cellular / molecular (subfield)
Methods: Statistics
Keywords: Dementia with Lewy bodies, Parkinson’s disease, Ultrastructure, Electron microscopy, Alpha-synuclein, Cortical Lewy bodies, Mitochondria
MeSH: Brain*, Lewy Bodies*, Lewy Body Disease*, Parkinson Disease*, Aged, Aged, 80 and over, alpha-Synuclein, Cerebral Cortex, Female, Humans, Male, Microscopy, Electron, Neurons, Substantia Nigra (* major topic)
Topic: Parkinson's Disease Mechanisms and Treatments (Neurology, Medicine), according to OpenAlex
Funding: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation); ZonMw; Stichting Woelse Waard; Parkinson Schweiz; EPFL Lausanne
Citations: cited by 2 papers (Europe PMC); 66 references in the paper

Abstract

Lewy body diseases, including Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), are defined by neuronal accumulation of misfolded α-synuclein (α-Syn), yet the ultrastructural diversity of these inclusions across brain regions and disease contexts remains unclear. Here, we applied large-scale correlative light and electron microscopy (CLEM) to map α-Syn pathology across cortical regions (entorhinal cortex, ENT; anterior cingulate cortex, AC; hippocampal CA2 region) and substantia nigra (SN) in clinically and pathologically confirmed PD and DLB donors. We identified pronounced regional heterogeneity in Lewy pathology, with cortical inclusions showing diverse maturation stages at the ultrastructural level, ranging from low-density fibrils interspersed with organelles to highly compact fibrillar inclusions. In the SN of DLB donors, we observed the full range of classical nigral LB morphologies previously described in PD. We additionally characterized diverse neuritic α-Syn pathologies in DLB and identified a distinct population of electron-dense, degenerating, α-Syn-positive cortical neurons not previously reported. Importantly, we found no significant difference in LB ultrastructure between PD and DLB in either cortical or nigral pathology. In contrast, quantitative analysis of > 10,000 mitochondria revealed disease- and region-specific signatures of altered mitochondrial homeostasis. PD showed increased mitochondrial density and enlargement in the SN, whereas DLB showed increased mitochondrial density only in the ENT. Mitochondrial enlargement was exclusive to PD. These findings indicate that LB ultrastructure alone does not distinguish PD from DLB; instead, region-specific mitochondrial phenotypes may better reflect disease identity and regional susceptibility. Overall, we provide a high-resolution framework for human Lewy pathology in PD and DLB, revealing that ultrastructural responses to α-Syn pathology are driven primarily by neuronal identity and regional vulnerability. Our results highlight the need for disease- and region-specific models that capture human phenotypes to advance mechanistic understanding and therapeutic targeting of synucleinopathies.

Supplementary Information: The online version contains supplementary material available at 10.1007/s00401-026-03039-w.

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

Repository

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

LBEM-CH/mitoanalyzer

License: GPL-3.0
State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Commit: 093440c4e4c5f189ea8124f91ce7c81f77f030ed, 8 December 2025
Languages: Jupyter (3)
Size: 12 files, 3 scripts
Software Heritage: not archived
Found in: “Code availability”
Holds: README, license file, 3 notebooks
Not found: CITATION.cff, environment file, tests, continuous integration, documentation
Tools: NumPy (3 files), OpenCV (2 files), tifffile (2 files)
Availability: 1 check, the latest on 27 September 2026: the link answers
  • 27 September 2026: the link answers
5 files
At the source: github.com/LBEM-CH/mitoanalyzer

Code availability

All codes are available on GitHub: https://github.com/LBEM-CH/mitoanalyzer

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

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:

  • 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 3 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

The raw EM micrographs and mitochondrial segmentation labels generated in this study have been deposited in the BioImageArchive (http://www.ebi.ac.uk/bioimage-archive) under accession number S-BIAD3729.

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 2, 28 September 2026

  • Publisher: n/a → Springer Science+Business Media

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 15 authors, 7 keywords, 14 MeSH terms, 5 funders, 65 references.

Cite

This paper

Shafiei, N., Proniakova, D., Simjanoska, M., Sjødal, A. M. R., Stähli, D., van den Heuvel, L., Di Fabrizio, M., Aaron, E., Kasas, S., Krause, M. S., Wittwer, M., Radecke, J., Stahlberg, H., van de Berg, W. D. J., & Lewis, A. J. (2026). Correlative ultrastructural mapping of Lewy pathology reveals regional diversity in Parkinson's and dementia with Lewy bodies. Acta neuropathologica, 152(1), 5. https://doi.org/10.1007/s00401-026-03039-w

BibTeX

@article{shafiei2026correlative,
author = {Shafiei, Notash and Proniakova, Daria and Simjanoska, Marija and Sjødal, Anniken Mathea Rafnum and Stähli, Daniel and van den Heuvel, Lukas and Di Fabrizio, Marta and Aaron, Eve and Kasas, Sandor and Krause, Mathis Solal and Wittwer, Mallory and Radecke, Julika and Stahlberg, Henning and van de Berg, Wilma D. J. and Lewis, Amanda J.},
title = {{Correlative ultrastructural mapping of Lewy pathology reveals regional diversity in Parkinson's and dementia with Lewy bodies}},
journal = {Acta neuropathologica},
year = {2026},
month = jul,
volume = {152},
number = {1},
pages = {5},
publisher = {Springer Science+Business Media},
issn = {0001-6322},
doi = {10.1007/s00401-026-03039-w},
url = {https://doi.org/10.1007/s00401-026-03039-w},
pmid = {42420695},
pmcid = {PMC13346217}
}

RIS

TY - JOUR
AU - Shafiei, Notash
AU - Proniakova, Daria
AU - Simjanoska, Marija
AU - Sjødal, Anniken Mathea Rafnum
AU - Stähli, Daniel
AU - van den Heuvel, Lukas
AU - Di Fabrizio, Marta
AU - Aaron, Eve
AU - Kasas, Sandor
AU - Krause, Mathis Solal
AU - Wittwer, Mallory
AU - Radecke, Julika
AU - Stahlberg, Henning
AU - van de Berg, Wilma D. J.
AU - Lewis, Amanda J.
TI - Correlative ultrastructural mapping of Lewy pathology reveals regional diversity in Parkinson's and dementia with Lewy bodies
T2 - Acta neuropathologica
J2 - Acta Neuropathol
PY - 2026
DA - 2026/07/08
VL - 152
IS - 1
SP - 5
SN - 0001-6322
PB - Springer Science+Business Media
DO - 10.1007/s00401-026-03039-w
UR - https://doi.org/10.1007/s00401-026-03039-w
LA - en
ER -

CSL-JSON

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"type": "article-journal",
"title": "Correlative ultrastructural mapping of Lewy pathology reveals regional diversity in Parkinson's and dementia with Lewy bodies",
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"author": [
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