OSCR

microRNA-132 attenuates inflammation in induced pluripotent stem cell-derived microglia from Alzheimer's disease patients.

Overview

Authors: Amber Penning1, Sarah Snoeck1, Olmo Ruiz Ormaechea1, Dilara Ayyildiz1, Oliver Polzer1,2, Martin Buitrago-Arango1, Raffaella Capobianco3, Fred de Winter1, Sriram Balusu4, Joost Verhaagen1, Carlos P Fitzsimons2, Constantin d’Ydewalle3, Paul J Lucassen2, Dieder Moechars3, Lujia Zhou3, Evgenia Salta1
ORCID iDs: Dilara Ayyildiz, Martin Buitrago-Arango
  1. Netherlands Institute for Neuroscience, Amsterdam, The Netherlands
  2. Brain Plasticity Group, Swammerdam Institute for Life Sciences, Faculty of Science, University of Amsterdam, Amsterdam, The Netherlands
  3. Neuroscience Discovery, Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium
  4. VIB-KU Leuven Center for Brain & Disease Research, Leuven, Belgium
Institutions: Netherlands Institute for Neuroscience (Netherlands); University of Amsterdam (Netherlands); Janssen (Belgium) (Belgium); VIB-KU Leuven Center for Brain & Disease Research (Belgium)
Journal: Acta neuropathologica communications, volume 14, issue 1, article 99
Dates: received 4 July 2025; accepted 10 January 2026; published online 7 March 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1186/s40478-026-02228-8 · PMID 41794876 · PMCID PMC13104464 · OpenAlex W7134182450
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: human (organism), mouse (organism), Alzheimer's / dementia (population), cellular / molecular (subfield)
Methods: Statistics, Preprocessing, Evoked potentials, fMRI & imaging
Keywords: microRNA, miR-132, iPSC, Microglia, Alzheimer’s disease
MeSH: Alzheimer Disease*, Induced Pluripotent Stem Cells*, Inflammation*, Microglia*, MicroRNAs*, Aged, Animals, Cells, Cultured, Disease Models, Animal, Female, Hippocampus, Humans, Male, Mice, Mice, Transgenic, Neurons (* major topic)
Topic: Neuroinflammation and Neurodegeneration Mechanisms (Neurology, Neuroscience), according to OpenAlex
Funding: Health∼Holland
Citations: cited by 3 papers (Europe PMC); 178 references in the paper

Abstract

Microglia, the resident immune cells of the brain, are increasingly recognized as key contributors to Alzheimer’s disease (AD) pathology. Multiple studies have identified microRNA-132 (miR-132) as one of the most significantly downregulated microRNAs in AD. Apart from well-established pleiotropic regulatory functions in neurons, previous evidence also suggested a role for miR-132 in regulating (neuro)inflammation. Yet, the precise mechanisms by which miR-132 impacts microglia remain unknown. In this study, we investigated the role of miR-132 in modulating microglial gene expression and function using gain- and loss-of-function approaches in human-induced pluripotent stem cell (iPSC)-derived microglia (iMGs) from both healthy controls and sporadic AD (sAD) patients. Our findings indicate that while miR-132 may not be indispensable for some baseline microglial functions, increasing its expression in sAD iMGs can reverse disease-associated gene expression changes and attenuate inflammatory responses. To further explore its therapeutic potential, we overexpressed miR-132 in hippocampal neurons of an AD mouse model, employing a clinically relevant adeno-associated viral (AAV) delivery method. miR-132 overexpression was well-tolerated and induced non-cell autonomous effects in microglia. This study sheds light into the regulatory role of miR-132 in microglia under both physiological and AD conditions, and emphasizes the importance of optimizing safe dosage parameters for future clinical applications.

Supplementary Information: The online version contains supplementary material available at 10.1186/s40478-026-02228-8.

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

Code

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Data

Datasets cited

Data availability

All data needed to evaluate the conclusions in the paper are present in the paper. The RNA sequencing data of this study will be available at GEO upon publication.

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, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 16 authors, 5 keywords, 16 MeSH terms, 1 funder, 178 references.

Cite

This paper

Penning, A., Snoeck, S., Ormaechea, O. R., Ayyildiz, D., Polzer, O., Buitrago-Arango, M., Capobianco, R., de Winter, F., Balusu, S., Verhaagen, J., Fitzsimons, C. P., d’Ydewalle, C., Lucassen, P. J., Moechars, D., Zhou, L., & Salta, E. (2026). microRNA-132 attenuates inflammation in induced pluripotent stem cell-derived microglia from Alzheimer's disease patients. Acta neuropathologica communications, 14(1), 99. https://doi.org/10.1186/s40478-026-02228-8

BibTeX

@article{penning2026microrna,
author = {Penning, Amber and Snoeck, Sarah and Ormaechea, Olmo Ruiz and Ayyildiz, Dilara and Polzer, Oliver and Buitrago-Arango, Martin and Capobianco, Raffaella and de Winter, Fred and Balusu, Sriram and Verhaagen, Joost and Fitzsimons, Carlos P and d’Ydewalle, Constantin and Lucassen, Paul J and Moechars, Dieder and Zhou, Lujia and Salta, Evgenia},
title = {{microRNA-132 attenuates inflammation in induced pluripotent stem cell-derived microglia from Alzheimer's disease patients}},
journal = {Acta neuropathologica communications},
year = {2026},
month = mar,
volume = {14},
number = {1},
pages = {99},
publisher = {BMC},
issn = {2051-5960},
doi = {10.1186/s40478-026-02228-8},
url = {https://doi.org/10.1186/s40478-026-02228-8},
pmid = {41794876},
pmcid = {PMC13104464}
}

RIS

TY - JOUR
AU - Penning, Amber
AU - Snoeck, Sarah
AU - Ormaechea, Olmo Ruiz
AU - Ayyildiz, Dilara
AU - Polzer, Oliver
AU - Buitrago-Arango, Martin
AU - Capobianco, Raffaella
AU - de Winter, Fred
AU - Balusu, Sriram
AU - Verhaagen, Joost
AU - Fitzsimons, Carlos P
AU - d’Ydewalle, Constantin
AU - Lucassen, Paul J
AU - Moechars, Dieder
AU - Zhou, Lujia
AU - Salta, Evgenia
TI - microRNA-132 attenuates inflammation in induced pluripotent stem cell-derived microglia from Alzheimer's disease patients
T2 - Acta neuropathologica communications
J2 - Acta Neuropathol Commun
PY - 2026
DA - 2026/03/07
VL - 14
IS - 1
SP - 99
SN - 2051-5960
PB - BMC
DO - 10.1186/s40478-026-02228-8
UR - https://doi.org/10.1186/s40478-026-02228-8
LA - en
ER -

CSL-JSON

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