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Targeting glial PD-1/PD-L1 restores microglial homeostasis and reduces neuronal hyperactivity in an Alzheimer's disease model.

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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

MATLAB · 58 lines · 1 KB · CC-BY-4.0

  1. %% microglia image
  2. tiffread
  3. for i=1:size(ans,2)
  4. microglia(:,:,i)=ans(i).data;
  5. end
  7. % figure;imshow(reference_image)
  8. figure;imagesc(microglia(:,:,1))
  9. reference=[350,350]
  10. reference=round(reference);
  12. mask=zeros(size(microglia(:,:,1)));
  13. mask(reference(2),reference(1))=1;
  14. % figure;imagesc(mask)
  16. % pixel
  17. pixel_resolution=0.2163;
  18. Disk_size=round(25/0.2163);
  21. se = strel('disk',Disk_size,0);
  22. mask(:,:,1) = imdilate(mask,se);
  23. mask2=mask;
  25. for i=2:3
  26. temp=mask2(:,:,i-1);
  27. se = strel('disk',Disk_size,0);
  28. mask2(:,:,i) = imdilate(temp,se);
  29. % mask(:,:,i)=mask2(i)-mask2(:,:,i-1);
  30. end
  32. for i=1:3
  33. if i==1
  34. ROI(:,:,i)=mask2(:,:,i);
  35. else
  36. ROI(:,:,i)=mask2(:,:,i)-mask2(:,:,i-1);
  37. end
  38. end
  40. %% ROI
  41. c_ROI=zeros(size(ROI(:,:,1)));
  42. for i=1:size(ROI,3)
  43. idx=find(ROI(:,:,i));
  44. c_ROI(idx)=i;
  45. end
  46. %% tracing
  48. for i=1:3
  49. idx=find(ROI(:,:,i));
  50. for k=1:size(microglia,3)
  51. temp=microglia(:,:,k);
  52. Tracing(k,i)=((sum(temp(idx))/size(idx,1))/255)*100;
  53. end
  54. end

Code1.m, under CC-BY-4.0 · at the source

Overview

Authors: Taeyoung Park1,2,3, Leechung Chang4,5, Seung Won Chung1,2,3, Seowoo Lee1,2,3, Sungjun Bae6, Carlo Condello7,8, Yong Ho Kim1,2,6,9,10,11,12, Jaecheol Lee6,9,13,14,15, Han-Joo Kim6, Ho-Keun Kwon4,5,16, Minah Suh1,2,3,6,9,17
ORCID iDs: Taeyoung Park, Leechung Chang, Seung Won Chung, Seowoo Lee, Sungjun Bae, Carlo Condello, Yong Ho Kim, Jaecheol Lee, Han-Joo Kim, Ho-Keun Kwon, Minah Suh
17 affiliations
  1. Department of Biomedical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
  2. Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Suwon 16419, Republic of Korea
  3. Department of Intelligent Precision Healthcare Convergence (IPHC), Fourth Stage of Brain Korea 21 Project (BK 21), Suwon 16419, Sungkyunkwan University, Republic of Korea
  4. Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
  5. Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
  6. IMNEWRUN Inc., Suwon 16419, Republic of Korea
  7. Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, CA 94158, USA
  8. Department of Neurology, University of California San Francisco, San Francisco, CA 94158, USA
  9. Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea
  10. SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University, Suwon 16419, Republic of Korea
  11. Department of Nano Science and Technology, Sungkyunkwan University, Suwon 16419, Republic of Korea
  12. Department of Nano Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
  13. School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea
  14. Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea
  15. Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon 16419, Republic of Korea
  16. Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
  17. KIST-SKKU Brain Research Center, Suwon 16419, Republic of Korea
Institutions: Institute for Basic Science (South Korea); Sungkyunkwan University (South Korea); Yonsei University (South Korea); University of California, San Francisco (United States); Yonsei University Health System (South Korea); Korea Institute of Science and Technology (South Korea)
Journal: Science advances, volume 12, issue 38, article eadx0731
Dates: received 28 February 2025; accepted 13 August 2026; published online 18 September 2026; in print September 2026
Type: Research article · Language: English
License: CC BY-NC
Identifiers: DOI 10.1126/sciadv.adx0731 · PMID 42758826 · PMCID PMC13588173 · OpenAlex W7213554415
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: human (organism), mouse (organism), Alzheimer's / dementia (population), cellular / molecular (subfield)
Methods: Spectral & time-frequency, Statistics, Smoothing, state filtering, decompositions, Evoked potentials, Connectivity, fMRI & imaging, Single-unit activity, calcium imaging, Physiology & signal measures
MeSH: Alzheimer Disease*, B7-H1 Antigen*, Homeostasis*, Microglia*, Neuroglia*, Neurons*, Programmed Cell Death 1 Receptor*, Animals, Astrocytes, Disease Models, Animal, Humans, Mice, Mice, Transgenic, Signal Transduction (* major topic)
Journal subjects: Neuroscience, Diseases and Disorders
Topic: Neuroinflammation and Neurodegeneration Mechanisms (Neurology, Neuroscience), according to OpenAlex
Funding: Institute for Basic Science (IBS) (IBS-R015-D1, IBS-R015-D2); Yonsei University College of Medicine (6-2020-0171); National Research Foundation of Korea (NRF) (RS-2025-00561456); Korea Dementia Research Project through the Korea Dementia Research Center (KDRC), funded by the Ministry of Health & Welfare and Ministry of Science and ICT (RS-2024-00344426); National Research Foundation of Korea (NRF) funded by the Korea government (MSIT) (2017R1A6A1A03015642, 2023R1A2C1004318, RS-2023-00302458, 2022M3A9I2017587, 2022M3E5E8018388); Institute of Information & communications Technology Planning & Evaluation (IITP) grant funded by the Korea government (MSIT) (2020-0-00261); Fourth Stage of Brain Korea 21 Project in Department of Intelligent Precision Healthcare, Sungkyunkwan University (SKKU) (RS-2022-0608-000); Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (RS-2024-00438443); KIST-SKKU Brain Research Center; IMNEWRUN Inc
Citations: not cited yet (Europe PMC); 75 references in the paper

Abstract

Alzheimer’s disease (AD) involves complex neuroimmune dysregulation, and the role of immune checkpoint pathways in regulating neuro–glial interactions and intrinsic glial homeostasis remains unclear. In AD, glial expression of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) is elevated in mouse models and human patients, suggesting involvement of immune checkpoint signaling in glial function. To define the role of this pathway in the AD brain, we locally modulated PD-1/PD-L1 signaling by intracortical anti-PD-L1 injection in 8–10-month-old 5xFAD mice, combined with in vivo two-photon imaging and quantitative functional analyses. Brain-intrinsic PD-L1 blockade reshaped the local glial microenvironment, restoring impaired microglial process convergence and increasing P2RY12 expression, a key marker of homeostatic function, with concomitant attenuation of aberrant neuronal hyperactivity. Astrocyte-specific PD-L1 knockdown produced similar effects, indicating a key role of astrocytic PD-L1 in regulating microglia–neuron interactions. These findings suggest that the glial PD-1/PD-L1 axis functions as a brain-intrinsic regulator of glial homeostasis linked to neuronal dysfunction in AD.

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

Repository

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

Zenodo 19411437

License: CC-BY-4.0
State: the link answers, verified on 26 September 2026
Evidence: files inventoried
Languages: MATLAB (3)
Size: 3 files, 3 scripts
Software Heritage: not checked
Found in: “Data, code, and materials availability:”
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Tools: Image Processing Toolbox (1 file)
Availability: 1 check, the latest on 26 September 2026: the link answers (HTTP 200)
  • 26 September 2026: the link answers (HTTP 200)
3 files
At the source: doi.org/10.5281/zenodo.19411437

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:

  • 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, code, and materials availability

All data and code needed to evaluate and reproduce the results in the paper are present in the paper and/or the Supplementary Materials and are available from https://doi.org/10.5281/zenodo.19411437. Viral vectors used for cell type-specific PD-L1 gene (CD274) silencing were generated for this study at the IBS Virus Facility and are available from the corresponding author M.S. upon request and following execution of a Material Transfer Agreement (MTA).

Reproduced under the paper's license (CC BY-NC), 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, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 11 authors, 14 MeSH terms, 10 funders, 75 references.

Cite

This paper

Park, T., Chang, L., Chung, S. W., Lee, S., Bae, S., Condello, C., Kim, Y. H., Lee, J., Kim, H.-J., Kwon, H.-K., & Suh, M. (2026). Targeting glial PD-1/PD-L1 restores microglial homeostasis and reduces neuronal hyperactivity in an Alzheimer's disease model. Science advances, 12(38), eadx0731. https://doi.org/10.1126/sciadv.adx0731

BibTeX

@article{park2026targeting,
author = {Park, Taeyoung and Chang, Leechung and Chung, Seung Won and Lee, Seowoo and Bae, Sungjun and Condello, Carlo and Kim, Yong Ho and Lee, Jaecheol and Kim, Han-Joo and Kwon, Ho-Keun and Suh, Minah},
title = {{Targeting glial PD-1/PD-L1 restores microglial homeostasis and reduces neuronal hyperactivity in an Alzheimer's disease model}},
journal = {Science advances},
year = {2026},
month = sep,
volume = {12},
number = {38},
pages = {eadx0731},
publisher = {American Association for the Advancement of Science},
issn = {2375-2548},
doi = {10.1126/sciadv.adx0731},
url = {https://doi.org/10.1126/sciadv.adx0731},
pmid = {42758826},
pmcid = {PMC13588173}
}

RIS

TY - JOUR
AU - Park, Taeyoung
AU - Chang, Leechung
AU - Chung, Seung Won
AU - Lee, Seowoo
AU - Bae, Sungjun
AU - Condello, Carlo
AU - Kim, Yong Ho
AU - Lee, Jaecheol
AU - Kim, Han-Joo
AU - Kwon, Ho-Keun
AU - Suh, Minah
TI - Targeting glial PD-1/PD-L1 restores microglial homeostasis and reduces neuronal hyperactivity in an Alzheimer's disease model
T2 - Science advances
J2 - Sci Adv
PY - 2026
DA - 2026/09/18
VL - 12
IS - 38
SP - eadx0731
SN - 2375-2548
PB - American Association for the Advancement of Science
DO - 10.1126/sciadv.adx0731
UR - https://doi.org/10.1126/sciadv.adx0731
LA - en
ER -

CSL-JSON

{
"id": "10.1126/sciadv.adx0731",
"type": "article-journal",
"title": "Targeting glial PD-1/PD-L1 restores microglial homeostasis and reduces neuronal hyperactivity in an Alzheimer's disease model",
"container-title": "Science advances",
"author": [
{
"family": "Park",
"given": "Taeyoung"
},
{
"family": "Chang",
"given": "Leechung"
},
{
"family": "Chung",
"given": "Seung Won"
},
{
"family": "Lee",
"given": "Seowoo"
},
{
"family": "Bae",
"given": "Sungjun"
},
{
"family": "Condello",
"given": "Carlo"
},
{
"family": "Kim",
"given": "Yong Ho"
},
{
"family": "Lee",
"given": "Jaecheol"
},
{
"family": "Kim",
"given": "Han-Joo"
},
{
"family": "Kwon",
"given": "Ho-Keun"
},
{
"family": "Suh",
"given": "Minah"
}
],
"container-title-short": "Sci Adv",
"volume": "12",
"issue": "38",
"page": "eadx0731",
"DOI": "10.1126/sciadv.adx0731",
"PMID": "42758826",
"PMCID": "PMC13588173",
"ISSN": "2375-2548",
"publisher": "American Association for the Advancement of Science",
"URL": "https://doi.org/10.1126/sciadv.adx0731",
"language": "en",
"issued": {
"date-parts": [
[
2026,
9,
18
]
]
}
}

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