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Inhaled xenon modulates microglia and ameliorates disease in mouse models of amyloidosis and tauopathy
Wesley Nogueira Brandão, Nimansha Jain, Zhuoran Yin, Kilian L. Kleemann, Madison Carpenter, Xin Bao, Javier Remolina Serrano, Eric Tycksen et al.. Science Translational Medicine, 2025-01-15
Topic: Brain proteins, microglia and lab models
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.
Key findings
- These results support the translation of Xe inhalation as an approach for treating AD.
Why it matters
In mouse models of amyloidosis and tauopathy, inhaled xenon changed microglia to an intermediate activation state, increased amyloid plaque compaction, reduced brain atrophy and neuroinflammation, and improved nest-building behavior. The authors say these results support translating xenon inhalation as a treatment for Alzheimer's disease, but this has not yet been shown in people.
Study details
- Evidence strengthLow
How this study scored 46/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Science Translational Medicine) |
| Journal's citation record | 3 / 4 | Science Translational Medicine: journal h-index 365 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 13 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 4.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 4.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 13 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Oleg Butovsky: h-index 67 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 3 / 3 | OpenAlex lists 11 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39813317) |
| Free to read | 2 / 2 | Free to read |
| Total | 46 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1126/scitranslmed.adk3690
- PubMed: 39813317
- Original source →
- Free full text: PubMed Central →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Brandão, W. N., Jain, N., Yin, Z., Kleemann, K. L., Carpenter, M., Bao, X., et al. (2025). Inhaled xenon modulates microglia and ameliorates disease in mouse models of amyloidosis and tauopathy. Science Translational Medicine. https://doi.org/10.1126/scitranslmed.adk3690
Vancouver
Brandão WN, Jain N, Yin Z, Kleemann KL, Carpenter M, Bao X, et al. Inhaled xenon modulates microglia and ameliorates disease in mouse models of amyloidosis and tauopathy. Science Translational Medicine. 2025. doi:10.1126/scitranslmed.adk3690. PMID: 39813317.
BibTeX
@article{brandao2025-39813317,
author = {Brandão, Wesley Nogueira and Jain, Nimansha and Yin, Zhuoran and Kleemann, Kilian L. and Carpenter, Madison and Bao, Xin and Serrano, Javier Remolina and Tycksen, Eric and others},
title = {{Inhaled xenon modulates microglia and ameliorates disease in mouse models of amyloidosis and tauopathy}},
journal = {Science Translational Medicine},
year = {2025},
doi = {10.1126/scitranslmed.adk3690},
pmid = {39813317},
url = {https://doi.org/10.1126/scitranslmed.adk3690}
}
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