Evidence map›Paper›PMID 39813317›Full record

ArticleScience translational medicine2025

Inhaled xenon modulates microglia and ameliorates disease in mouse models of amyloidosis and tauopathy.

Wesley Brandao, Nimansha Jain, Zhuoran Yin, Kilian L Kleemann, Madison Carpenter, Xin Bao, Javier R Serrano, Eric Tycksen, Ana Durao, Jen-Li Barry and 19 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06945614 (A Proof-of-Concept, Exploratory Clinical Study to Assess Safety and Efficacy of Xenon Gas Inhalation to Control Neuroinflammation in Healthy Human Subjects), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT06945614 phase1recruitingnot on this map

A Proof-of-Concept, Exploratory Clinical Study to Assess Safety and Efficacy of Xenon Gas Inhalation to Control Neuroinflammation in Healthy Human Subjects

TypeinterventionalSponsorGeneral Biophysics LLCRan2025 to 2025Enrolled16ConditionsHealthy Volunteer StudyArmsXenon gas inhalation
3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Immune dysfunction in Alzheimer disease.Nature reviews. Neuroscience · 2026
    Review
  5. Article
  6. Signs of Alzheimer's Disease: Tied to Aging.International journal of molecular sciences · 2025
    Review
  7. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors.

Wesley BrandaoDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Nimansha JainDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0001-5360-5466
Zhuoran YinDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-8525-0062
Kilian L KleemannDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-2753-6804
Madison CarpenterDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0009-0003-5024-6359
Xin BaoDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Javier R SerranoDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0002-5937-0212
Eric TycksenMcDonnell Genome Institute, Genome Technology Access Center, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0001-6362-0141
Ana DuraoDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Jen-Li BarryDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Caroline BaufeldDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Dilansu GuneykayaDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Xiaoming ZhangDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-2654-3620
Alexandra LitvinchukDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Hong JiangDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0001-6480-7469
Neta RosenzweigDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-8668-6466
Kristen M PittsDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-7049-0883
Michael AronchikDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Taha YahyaDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Tian CaoDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0009-0000-4664-2285
Marcelo Kenzo TakahashiDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-1091-0449
Rajesh KrishnanDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Hayk DavtyanDepartment of Neurobiology and Behavior, University of California, Irvine, CA, USA.ORCID 0000-0001-8554-6456
Jason D UlrichDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0002-4743-926X
Mathew Blurton-JonesDepartment of Neurobiology and Behavior, University of California, Irvine, CA, USA.ORCID 0000-0002-7770-7157
Ilya IlinGeneral Biophysics LLC, Boston, MA, USA.ORCID 0000-0002-7779-5150
Howard L WeinerDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-0203-9681
David M HoltzmanDepartment of Neurology, Washington University School of Medicine, St. Louis, MO, USA.ORCID 0000-0002-3400-0856
Oleg ButovskyDepartment of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-0186-8867

Funding

Project 4 (Genetic modifiers for APOE-associated Alzheimer's disease pathogenesis)U19AG069701 · NIA · MAYO CLINIC JACKSONVILLE · PI Andrea Soranno · 2021 to 2026
$42.0M
The Alzheimer's Disease Research Center at the University of California, IrvineP30AG066519 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Elizabeth Head · 2020 to 2026
$27.9M
Effect of APOE on CNS Neurons: Role of LRPRF1NS090934 · NINDS · WASHINGTON UNIVERSITY · PI HOLTZMAN, DAVID M. · 2020 to 2025
$6.5M
Targeting TGFb/IFNy-IRF8 Signaling to Modulate Monocytes and their Crosstalk with Microglia and Astrocytes to Treat Multiple SclerosisR01NS088137 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI Oleg Butovsky · 2014 to 2026
$4.9M
Targeting the miR-155 and APOE-TREM2 pathways to restore dysfunctional microglia in Alzheimer’s diseaseR01AG054672 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI BUTOVSKY, OLEG, IKEZU, TSUNEYA · 2017 to 2021
$4.1M
Effect of APOE on CNS Neurons: Role of LRPR01NS090934 · NINDS · WASHINGTON UNIVERSITY · PI HOLTZMAN, DAVID M. · 2014 to 2018
$3.0M
Microglial mechanisms of postoperative CNS inflammation and cognitive declineR01AG051812 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI BUTOVSKY, OLEG, CROSBY, GREGORY · 2016 to 2020
$2.7M
Therapeutic Strategy to Treat Alzheimer's Disease by VGF Delivery into BrainR01AG083981 · NIA · NORTH DAKOTA STATE UNIVERSITY · PI Takahisa Kanekiyo, Jagdish Singh · 2023 to 2026
$2.4M
Xenon gas treatment to modulate microglia in neurodegenerative diseasesR41AG073059 · NIA · GENERAL BIOPHYSICS, LLC · PI BUTOVSKY, OLEG, ILIN, ILYA · 2021 to 2022
$813k
NIA NIH HHS P30 AG066519NIA NIH HHS R01 AG051812NIA NIH HHS R01 AG054672NIA NIH HHS R01 AG083981NIA NIH HHS R41 AG073059NIA NIH HHS U19 AG069701NINDS NIH HHS R01 NS088137NINDS NIH HHS R01 NS090934NINDS NIH HHS RF1 NS090934
6 · The paper itself

Abstract

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. Antiamyloid antibody treatments modestly slow disease progression in mild dementia due to AD. Emerging evidence shows that homeostatic dysregulation of the brain immune system, especially that orchestrated by microglia, plays an important role in disease onset and progression. Thus, a major question is how to modulate the phenotype and function of microglia to treat AD. Xenon (Xe) gas is a noble gas used in human patients as an anesthetic and a neuroprotectant used for treating brain injuries. Xe penetrates the blood-brain barrier, which could make it an effective therapeutic. To assess the effect of Xe on microglia and AD pathology, we designed a custom Xe inhalation chamber and treated several mouse models of AD with Xe gas. Xe treatment induced mouse microglia to adopt an intermediate activation state that we have termed pre-neurodegenerative microglia (pre-MGnD). This microglial phenotypic transition was observed in mouse models of acute neurodegeneration and amyloidosis (APP/PS1 and 5xFAD mice) and tauopathy (P301S mice). This microglial state enhanced amyloid plaque compaction and reduced dystrophic neurites in the APP/PS1 and 5xFAD mouse models. Moreover, Xe inhalation reduced brain atrophy and neuroinflammation and improved nest-building behavior in P301S mice. Mechanistically, Xe inhalation induced homeostatic brain microglia toward a pre-MGnD state through IFN-γ signaling that maintained the microglial phagocytic response in APP/PS1 and 5xFAD mice while suppressing the microglial proinflammatory phenotype in P301S mice. These results support the translation of Xe inhalation as an approach for treating AD.

Indexed as

AmyloidosisMicrogliaTauopathiesXenonAdministration, InhalationAlzheimer DiseaseAnimalsDisease Models, AnimalHumansMiceMice, Inbred C57BLMice, TransgenicPlaque, AmyloidXenon

Identifiers

PMID39813317
PMCPMC13006031

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.