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Tracking tau and cellular responses in human iPSC-microglia: from uptake to seedable secretion, including in extracellular vesicles.

Code ↔ Paper

6 matches between paragraphs of the paper and lines of its authors' code, computed by the harvester (lexical-v1). Click a colored paragraph or line to see its counterpart.

The 6 matches
  1. [1] § RESULTS › Tau fibril challenge promotes downregulation of homeostatic and major histocompatibility complex (MHC) gene expression and upregulation of chemokine gene expression in iMGL ↔ Recombinant_tau_figures.R, lines 269–327 · score 0.73 · CD2AP, AD GWAS, MS4A6A, Log2FC, LILRB2, TNIP1
  2. [2] § RESULTS › Tau fibril challenge promotes downregulation of homeostatic and major histocompatibility complex (MHC) gene expression and upregulation of chemokine gene expression in iMGL ↔ Recombinant_tau_figures.R, lines 269–327 · score 0.72 · AD GWAS genes, CD2AP, MS4A6A, Log2FC, LILRB2, TNIP1
  3. [3] § RESULTS › Tau fibril challenge promotes downregulation of homeostatic and major histocompatibility complex (MHC) gene expression and upregulation of chemokine gene expression in iMGL ↔ Human_tau_figure.R, lines 97–155 · score 0.64 · cytokine response microglia, interferon response microglia, CRM, HOM, IRM, HLA
  4. [4] § RESULTS › Tau fibril challenge promotes downregulation of homeostatic and major histocompatibility complex (MHC) gene expression and upregulation of chemokine gene expression in iMGL ↔ Recombinant_tau_figures.R, lines 139–196 · score 0.64 · cytokine response microglia, interferon response microglia, CRM, HOM, IRM, HLA
  5. [5] § RESULTS › Tau fibril challenge promotes downregulation of homeostatic and major histocompatibility complex (MHC) gene expression and upregulation of chemokine gene expression in iMGL ↔ Human_tau_figure.R, lines 97–155 · score 0.63 · P2RY12, IL1B, CX3CR1, CCL2, cytokine, tau
  6. [6] § RESULTS › Tau fibril challenge promotes downregulation of homeostatic and major histocompatibility complex (MHC) gene expression and upregulation of chemokine gene expression in iMGL ↔ Recombinant_tau_figures.R, lines 139–196 · score 0.63 · P2RY12, IL1B, CX3CR1, CCL2, cytokine, tau

Paper

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

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The authors' code

R · 329 lines · 14 KB · MIT · 4 matches

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It can be read at the source: Recombinant_tau_figures.R.

Overview

Authors: Maria Kreger Karabova1, Anna del Ser‐Badia1, Anne Hedegaard1, Sam J Washer1, Zeynep Baykam1, Darragh P O'Brien2, Iolanda Vendrell2, Svenja S Hester2, Roman Fischer2, Errin Johnson3, Charlotte E Melia3, Teige R S Matthews‐Palmer4,5, Rishi Matadeen4, Alessia Santambrogio6, Michael A Metrick II6, Michele Vendruscolo6, Sophie Keeling7, Kimberly Ai Xian Cheam7, William A McEwan7, Kenneth S Kosik8,9, Theresa A Day10, William S James1, Sally A Cowley1
ORCID iDs: Maria Kreger Karabova, Sally A Cowley
  1. James and Lillian Martin Centre for Stem Cell Research, Sir William Dunn School of Pathology, University of Oxford, Oxford, UK
  2. Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK
  3. Sir William Dunn School of Pathology, University of Oxford, Oxford, UK
  4. Central Oxford Structural Molecular Imaging Centre, Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, University of Oxford, Oxford, UK
  5. Current affiliation: Division of Structural Biology, The Institute of Cancer Research (ICR), London, UK
  6. Centre for Misfolding Diseases, Yusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK
  7. UK Dementia Research Institute at the University of Cambridge, Cambridge, UK
  8. Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, California, USA
  9. Department of Molecular, Cell and Developmental Biology, University of California Santa Barbara, Santa Barbara, California, USA
  10. Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, USA
Institutions: University of Oxford (United Kingdom); Institute of Cancer Research (United Kingdom); University of Cambridge (United Kingdom); UK Dementia Research Institute (United Kingdom); University of California, Santa Barbara (United States); Eli Lilly (United States) (United States)
Journal: Alzheimer's & dementia : the journal of the Alzheimer's Association, volume 22, issue 4, article e71337
Dates: received 16 October 2025; accepted 5 March 2026; published online 6 April 2026; in print April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1002/alz.71337 · PMID 41943483 · PMCID PMC13053939 · OpenAlex W7151345844
Open access: hybrid, a free copy (OpenAlex)
Status: code verified
Categories: genetics / omics (modality), histology / microscopy (modality), human (organism), Alzheimer's / dementia (population), cellular / molecular (subfield)
Methods: Spectral & time-frequency, Statistics
Keywords: cryo‐electron microscopy, extracellular vesicle, induced pluripotent stem cells, lipoprotein receptor‐related protein 1, LRP1, microglia, phospho‐proteome, tau
MeSH: Extracellular Vesicles*, Induced Pluripotent Stem Cells*, Microglia*, tau Proteins*, Alzheimer Disease, Humans, Low Density Lipoprotein Receptor-Related Protein-1 (* major topic)
Topic: Neuroinflammation and Neurodegeneration Mechanisms (Neurology, Neuroscience), according to OpenAlex
Funding: The James Martin 21st Century Research Foundation
Citations: cited by 1 paper (Europe PMC); 107 references in the paper

Abstract

INTRODUCTION: Microglia have been implicated in the templated spread of tau aggregates in tauopathies through mouse studies. However, it is unclear whether these findings translate to human disease.

METHODS: We challenged human induced pluripotent stem cell (iPSC)‐derived microglia‐like‐cells (iMGL) with monomeric and fibrillar recombinant tau and tau purified from Alzheimer's patient brains, examining in detail the uptake, processing, release, and seeding of tau by microglia.

RESULTS: iMGL take up tau via lipoprotein receptor‐related protein 1 (LRP)1 and heparan sulfate proteoglycans, with leucine‐rich repeat kinase 2 affecting LRP1 trafficking. Monomeric tau is digested effectively with minimal effects on iMGL, but recombinant or brain‐derived tau fibrils induce chemokine/interferon response subtypes, alongside downregulation of homeostatic genes. Fibrillar tau is degradation‐resistant, can escape into the cytoplasm, and becomes phosphorylated on two specific residues. iMGL release partially digested fibrillar tau, including in extracellular vesicles, visualized by cryo‐electron microscopy, that seed aggregation in neurons.

DISCUSSION: Our study reveals new insights into human microglial responses to tau, highlighting opportunities to limit pathogenic tau spread.

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

Repository

Its files are read in the Code ↔ Paper reader above, with 6 matches between paragraphs and lines of code.

s-washer/karabova_2025_tracking_tau_and_cellular_responses_in_microglia_rnaseq

License: MIT
State: the link answers, verified on 28 September 2026
Evidence: files inventoried
Commit: 8193af879f931b5ac02dafed986af76d5e9d3b27, 4 February 2025
Languages: R (4)
Size: 106 files, 4 scripts
Software Heritage: not archived
Found in: “CODE AVAILABILITY”
Holds: README
Not found: license file, CITATION.cff, environment file, tests, continuous integration, documentation
Tools: cowplot (4 files), DESeq2 (4 files), ggplot2 (4 files), ggpubr (4 files), pheatmap (4 files), tidyverse (4 files), reshape2 (1 file)
Availability: 1 check, the latest on 28 September 2026: the link answers
  • 28 September 2026: the link answers
5 files, not copied: shown from their source

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At the source: github.com/S-Washer/Karabova_2025_Tracking_tau_and_cellular_responses_in_microglia_RNAseq/tree/main

Code availability

All code for RNAseq is available at https://github.com/S‐Washer/Karabova_2025_Tracking_tau_and_cellular_responses_in_microglia_RNAseq/tree/main (https://github.com/S-Washer/Karabova_2025_Tracking_tau_and_cellular_responses_in_microglia_RNAseq/tree/main)

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;
  • 4 scripts, each with its path and the digest of its content;
  • 6 matches between paragraphs of the paper and lines of the code (method lexical-v1);
  • 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

Datasets cited

Data availability statement

Raw RNA‐seq .fastq, processed kallisto abundance.tsv, and abundance.h5 files have been deposited in Gene Expression Omnibus (GSE291195 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291195)). The mass spectrometry data have been deposited in ProteomeXchange (PRIDE database).

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, issue, pages, dates, 23 authors, 8 keywords, 7 MeSH terms, 1 funder, 107 references.

Cite

This paper

Karabova, M. K., del Ser‐Badia, A., Hedegaard, A., Washer, S. J., Baykam, Z., O'Brien, D. P., Vendrell, I., Hester, S. S., Fischer, R., Johnson, E., Melia, C. E., Matthews‐Palmer, T. R. S., Matadeen, R., Santambrogio, A., Metrick, M. A., Vendruscolo, M., Keeling, S., Cheam, K. A. X., McEwan, W. A., . . . Cowley, S. A. (2026). Tracking tau and cellular responses in human iPSC-microglia: from uptake to seedable secretion, including in extracellular vesicles. Alzheimer's & dementia : the journal of the Alzheimer's Association, 22(4), e71337. https://doi.org/10.1002/alz.71337

BibTeX

@article{karabova2026tracking,
author = {Karabova, Maria Kreger and del Ser‐Badia, Anna and Hedegaard, Anne and Washer, Sam J and Baykam, Zeynep and O'Brien, Darragh P and Vendrell, Iolanda and Hester, Svenja S and Fischer, Roman and Johnson, Errin and Melia, Charlotte E and Matthews‐Palmer, Teige R S and Matadeen, Rishi and Santambrogio, Alessia and Metrick, Michael A and Vendruscolo, Michele and Keeling, Sophie and Cheam, Kimberly Ai Xian and McEwan, William A and Kosik, Kenneth S and Day, Theresa A and James, William S and Cowley, Sally A},
title = {{Tracking tau and cellular responses in human iPSC-microglia: from uptake to seedable secretion, including in extracellular vesicles}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2026},
month = apr,
volume = {22},
number = {4},
pages = {e71337},
publisher = {Wiley},
issn = {1552-5260},
doi = {10.1002/alz.71337},
url = {https://doi.org/10.1002/alz.71337},
pmid = {41943483},
pmcid = {PMC13053939}
}

RIS

TY - JOUR
AU - Karabova, Maria Kreger
AU - del Ser‐Badia, Anna
AU - Hedegaard, Anne
AU - Washer, Sam J
AU - Baykam, Zeynep
AU - O'Brien, Darragh P
AU - Vendrell, Iolanda
AU - Hester, Svenja S
AU - Fischer, Roman
AU - Johnson, Errin
AU - Melia, Charlotte E
AU - Matthews‐Palmer, Teige R S
AU - Matadeen, Rishi
AU - Santambrogio, Alessia
AU - Metrick, Michael A
AU - Vendruscolo, Michele
AU - Keeling, Sophie
AU - Cheam, Kimberly Ai Xian
AU - McEwan, William A
AU - Kosik, Kenneth S
AU - Day, Theresa A
AU - James, William S
AU - Cowley, Sally A
TI - Tracking tau and cellular responses in human iPSC-microglia: from uptake to seedable secretion, including in extracellular vesicles
T2 - Alzheimer's & dementia : the journal of the Alzheimer's Association
J2 - Alzheimers Dement
PY - 2026
DA - 2026/04/01
VL - 22
IS - 4
SP - e71337
SN - 1552-5260
PB - Wiley
DO - 10.1002/alz.71337
UR - https://doi.org/10.1002/alz.71337
LA - en
ER -

CSL-JSON

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