Heterogenous microglial reactivity contrasts with stable vascular transcriptional programs in mouse models of Alzheimer's, CADASIL, and Traumatic Brain Injury.
Overview
and 6 other authors
R Torp1,4, U Lendahl13, H Karlström1, E P Thelin7,14, P Nilsson1, M Vanlandewijck2,1014 affiliations
- Department of Neurobiology Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
- Pediatric Research Institute, University of Padua, Padua, Italy
- Department of Anatomy, Institute of Basic Medical Sciences, Oslo, Norway
- MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht, the Netherlands
- Cardio-Thoracic Surgery Department, Heart and Vascular Centre, Maastricht University Medical Centre (MUMC+), Maastricht, the Netherlands
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
- Medical Unit Neurosurgery, Karolinska University Hospital, Stockholm, Sweden
- Department of Medical Sciences, Acquired Brain Injury, Uppsala Universitet, Uppsala, Sweden
- Department of Immunology, Genetics and Pathology, Uppsala universitet, Uppsala, Sweden
- Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands
- Department of Public Health and Caring Sciences, Uppsala universitet, Uppsala, Sweden
- Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden
- Medical Unit Neurology, Karolinska University Hospital, Stockholm, Sweden
Abstract
The extent to which the cerebrovasculature is affected in various brain disorders is still not well understood. To address this, we established a transcriptomic repository of major vascular cell types and microglia to compare the global transcriptomic response in mouse models of three human brain disorders linked to neuroinflammation and associated vascular reactivity: Alzheimer’s disease (AD), traumatic brain injury (TBI), and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Single-cell analysis of >250,000 cells at different disease stages led to identification of two previously unknown vascular cell subtypes, expanded the endothelial zonation spectrum and allowed for a detailed analysis of the cellular and molecular responses. Surprisingly, most vascular cell types lacked major transcriptomic changes across the three conditions, while microglia exhibited significant, disease-specific transcriptional changes. Notably, microglial responses converged between late-stage TBI and AD, offering insights into the predisposition for neurodegeneration following TBI.
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Data
Datasets cited
- geo:GSE318960, at NCBI GEO; found in “Data availability”
Data availability
The single cell and spatial data generated in this study have been deposited in the GEO gene expression omnibus database under accession codes GSE318960 (https://
Reproduced under the paper's license (CC BY), from the paper cited above.
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Version 2, 28 September 2026
- Funding: added Karolinska Institutet
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 26 authors, 3 keywords, 13 MeSH terms, 77 references, 25 RRIDs.
Cite
This paper
Bjørnholm, K. D., Li, H., Del Gaudio, F., Mocci, G., Shao, W., Baldisseri, E., Rao, S. B., Lindblad, C., Fletcher-Sandersjöö, A., Vázquez-Liébanas, E., Pietilä, R., Muhl, L., Jiang, R., Kalantzi, C., Cheung, J., Jin, S., Svensson, M., Lesnik Oberstein, S. A. J., Syvänen, S., . . . Vanlandewijck, M. (2026). Heterogenous microglial reactivity contrasts with stable vascular transcriptional programs in mouse models of Alzheimer's, CADASIL, and Traumatic Brain Injury. Nature communications, 17(1), 6392. https://
BibTeX
@article{bjrnholm2026het
author = {Bjørnholm, K D and Li, H and Del Gaudio, F and Mocci, G and Shao, W and Baldisseri, E and Rao, S B and Lindblad, C and Fletcher-Sandersjöö, A and Vázquez-Liébanas, E and Pietilä, R and Muhl, L and Jiang, R and Kalantzi, C and Cheung, J and Jin, S and Svensson, M and Lesnik Oberstein, S A J and Syvänen, S and Mäe, M A and Torp, R and Lendahl, U and Karlström, H and Thelin, E P and Nilsson, P and Vanlandewijck, M},
title = {{Heterogenous microglial reactivity contrasts with stable vascular transcriptional programs in mouse models of Alzheimer's, CADASIL, and Traumatic Brain Injury}},
journal = {Nature communications},
year = {2026},
month = jul,
volume = {17},
number = {1},
pages = {6392},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/
url = {https://
pmid = {42463666},
pmcid = {PMC13377223}
}
RIS
TY - JOUR
AU - Bjørnholm, K D
AU - Li, H
AU - Del Gaudio, F
AU - Mocci, G
AU - Shao, W
AU - Baldisseri, E
AU - Rao, S B
AU - Lindblad, C
AU - Fletcher-Sandersjöö, A
AU - Vázquez-Liébanas, E
AU - Pietilä, R
AU - Muhl, L
AU - Jiang, R
AU - Kalantzi, C
AU - Cheung, J
AU - Jin, S
AU - Svensson, M
AU - Lesnik Oberstein, S A J
AU - Syvänen, S
AU - Mäe, M A
AU - Torp, R
AU - Lendahl, U
AU - Karlström, H
AU - Thelin, E P
AU - Nilsson, P
AU - Vanlandewijck, M
TI - Heterogenous microglial reactivity contrasts with stable vascular transcriptional programs in mouse models of Alzheimer's, CADASIL, and Traumatic Brain Injury
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/
VL - 17
IS - 1
SP - 6392
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/
UR - https://
LA - en
ER -
CSL-JSON
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