The PM20D1-OLE pathway induces microglia rewiring to ameliorate Alzheimer disease.
Overview
- Laboratory of Functional Epi-Genomics of Aging and Alzheimer’s disease, Instituto de Neurociencias, Universidad Miguel Hernández-Consejo Superior de Investigaciones Científicas (UMH-CSIC), Alicante, Spain
- Laboratory of Neuroepigenetics, School of Life Sciences, Brain Mind Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
- Laboratory of Integrative Systems Physiology, Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
- Laboratory of Molecular and Chemical Biology of Neurodegeneration, School of Life Sciences, Brain Mind Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
Abstract
There is increasing evidence of microglia participation in Alzheimer’s disease (AD), which incentives their modulation to intercept the disease. Here, we describe a new mechanism by which the recently AD-associated Peptidase M20 Domain Containing 1 (PM20D1) instructs microglia to tackle AD. We show that the PM20D1-derived N-oleoyl-Leucine (OLE) improves AD pathologies in two animal models of AD. OLE induces microglia association with amyloid beta (Aβ) plaques, reduce their size, number and toxicity, and leads to enhanced neuroprotection and cognition. Furthermore, OLE also increases Aβ chemotaxis and clearance in microglia cultures and enhances cell viability in neurons subjected to AD-related stressors. Finally, we also find evidence for a PM20D1- and OLE-mediated microglia association with amyloid plaques and neuroprotection in human AD brains. In sum, our results provide further insight into the protective role of PM20D1 in AD and support the use of OLE as a microglia-modifying treatment for AD.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.
The paper's code and data availability statement is in the Data section.
Tracing map
A tracing map links a paper to the code its authors published: this paper has none (its code is available on request), so it has no map.
Data
Datasets cited
- geo:GSE33000, at NCBI GEO; found in the text, “OLE RNA expression signatures are conserved in…”
Data availability
The raw data generated in this study is available in the Gene Expression Omnibus repository (GSE214352 (https://
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, 13 authors, 2 keywords, 19 MeSH terms, 3 funders, 99 references.
Cite
This paper
Pozzi-Ruiz, V., Giner de Gracia, A., Glauser, L., Romani, M., Gunter-Rahman, F., González-Ramón, A., Haj-Yahya, M., Kolla, R., Burns, A. M., Lashuel, H. A., Auwerx, J., Gräff, J., & Sanchez-Mut, J. V. (2026). The PM20D1-OLE pathway induces microglia rewiring to ameliorate Alzheimer disease. Cell death & disease, 17(1), 561. https://
BibTeX
@article{pozziruiz2026pm
author = {Pozzi-Ruiz, Victoria and Giner de Gracia, Aida and Glauser, Liliane and Romani, Mario and Gunter-Rahman, Fatima and González-Ramón, Alejandro and Haj-Yahya, Mahmood and Kolla, Rajasekhar and Burns, Allison M and Lashuel, Hilal A and Auwerx, Johan and Gräff, Johannes and Sanchez-Mut, Jose V},
title = {{The PM20D1-OLE pathway induces microglia rewiring to ameliorate Alzheimer disease}},
journal = {Cell death \& disease},
year = {2026},
month = apr,
volume = {17},
number = {1},
pages = {561},
publisher = {Nature Publishing Group},
issn = {2041-4889},
doi = {10.1038/
url = {https://
pmid = {42045164},
pmcid = {PMC13254073}
}
RIS
TY - JOUR
AU - Pozzi-Ruiz, Victoria
AU - Giner de Gracia, Aida
AU - Glauser, Liliane
AU - Romani, Mario
AU - Gunter-Rahman, Fatima
AU - González-Ramón, Alejandro
AU - Haj-Yahya, Mahmood
AU - Kolla, Rajasekhar
AU - Burns, Allison M
AU - Lashuel, Hilal A
AU - Auwerx, Johan
AU - Gräff, Johannes
AU - Sanchez-Mut, Jose V
TI - The PM20D1-OLE pathway induces microglia rewiring to ameliorate Alzheimer disease
T2 - Cell death & disease
J2 - Cell Death Dis
PY - 2026
DA - 2026/
VL - 17
IS - 1
SP - 561
SN - 2041-4889
PB - Nature Publishing Group
DO - 10.1038/
UR - https://
LA - en
ER -
CSL-JSON
{
"id": "10.1038/
"type": "article-journal",
"title": "The PM20D1-OLE pathway induces microglia rewiring to ameliorate Alzheimer disease",
"container-title": "Cell death & disease",
"author": [
{
"family": "Pozzi-Ruiz",
"given": "Victoria"
},
{
"family": "Giner de Gracia",
"given": "Aida"
},
{
"family": "Glauser",
"given": "Liliane"
},
{
"family": "Romani",
"given": "Mario"
},
{
"family": "Gunter-Rahman",
"given": "Fatima"
},
{
"family": "González-Ramón",
"given": "Alejandro"
},
{
"family": "Haj-Yahya",
"given": "Mahmood"
},
{
"family": "Kolla",
"given": "Rajasekhar"
},
{
"family": "Burns",
"given": "Allison M"
},
{
"family": "Lashuel",
"given": "Hilal A"
},
{
"family": "Auwerx",
"given": "Johan"
},
{
"family": "Gräff",
"given": "Johannes"
},
{
"family": "Sanchez-Mut",
"given": "Jose V"
}
],
"container-title-short":
"volume": "17",
"issue": "1",
"page": "561",
"DOI": "10.1038/
"PMID": "42045164",
"PMCID": "PMC13254073",
"ISSN": "2041-4889",
"publisher": "Nature Publishing Group",
"URL": "https://
"language": "en",
"issued": {
"date-parts": [
[
2026,
4,
27
]
]
}
}
Similar papers
The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.
- [1] doi:10.3390/biomedicines14050998 [code]
- Integrative Multi-Omics and Machine Learning Analysis Identifies Therapeutic Targets and Drug Repurposing Candidates for Alzheimer's Disease.Journal: BiomedicinesIn common: NCBI GEO GSE33000, Alzheimer's / dementia, genetics / omics, cellular / molecular, 3 references
- [2] doi:10.1186/s12974-026-03897-x [code]
- Ischemic injury triggers a protective microglial phenotype in models of Aβ pathology.Journal: Journal of neuroinflammationIn common: Alzheimer's / dementia, mouse, cellular / molecular, 4 references
- [3] doi:10.3390/ijms27146196
- Investigation of the Potential Neuroprotective Mechanisms of &
lt;i& gt;Acalypha indica& lt;/ i& gt; Against Alzheimer's Disease by Integrated Bioinformatics Analysis. Journal: International journal of molecular sciencesIn common: NCBI GEO GSE33000, Alzheimer's / dementia, genetics / omics, cellular / molecular, 1 reference - [4] doi:10.1038/s41398-026-04199-9 [code]
- Immune cell-specific genetic architecture of Alzheimer's disease revealed by multi-omics analysis for therapeutic target discovery and prioritization.Journal: Translational psychiatryIn common: Alzheimer's / dementia, genetics / omics, cellular / molecular, 3 references
- [5] doi:10.3389/fimmu.2026.1937738
- Multi-regional transcriptomic analysis reveals early nociceptive and neuroinflammatory alterations in APP/
PS1 mice. Journal: Frontiers in immunologyIn common: NCBI GEO GSE33000, Alzheimer's / dementia, genetics / omics, mouse, 1 other category - [6] doi:10.1186/s13024-026-00948-y
- Dual orexin receptor antagonism with lemborexant enhances microglial clearance of β-amyloid in mice.Journal: Molecular neurodegenerationIn common: Alzheimer's / dementia, genetics / omics, mouse, 1 other category, 3 references
- [7] doi:10.1007/s00401-026-03036-z
- Mechanisms of increased Alzheimer's disease pathology with R47H and R62H TREM2 variants.Journal: Acta neuropathologicaIn common: Alzheimer's / dementia, genetics / omics, cellular / molecular, 3 references
- [8] doi:10.1038/s41467-026-73007-1 [code]
- Single-nucleus epigenomic dysregulation unmasks genetic risk-associated neurodegenerative glia states.Journal: Nature communicationsIn common: Alzheimer's / dementia, genetics / omics, other condition, 1 other category, 3 references
- [9] doi:10.1038/s41467-026-70374-7 [code]
- scTWAS: a powerful statistical framework for single-cell transcriptome-wide association studies.Journal: Nature communicationsIn common: Alzheimer's / dementia, genetics / omics, cellular / molecular, 3 references
- [10] doi:10.1371/journal.pcbi.1014074 [code]
- Interpretable integration of unpaired multi-omics for Alzheimer's diagnosis via cross-modal transformer reconstruction.Journal: PLoS computational biologyIn common: NCBI GEO GSE33000, Alzheimer's / dementia, genetics / omics
Contribute
The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.
Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.
Claim this paper
Correct its record
Say what each link of this record is, remove the ones that are not the paper's, add the ones that are missing. The correction becomes a new version of the record, in its Versions section.
Request its removal
To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).
Discussion, reproductions, activity
Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.
Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.
Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.