Xenon is a noble gas known for being inert, or unable to participate in nearly all chemical reactions. However, the gas does have several applications, including in lighting, mass spectrometry, and general anesthesia.1 New research recently published in the journal Science Translational Medicine suggests that xenon may have other applications in medicine due to its potential benefits for the brain, leading to interest in studying it in the context of treating Alzheimer’s disease.2
Current treatments for Alzheimer’s, which affects 50 million people worldwide,3 target the protein amyloid-beta, which builds up in plaques in the brains of most patients with the disease. Though some drugs in this class, including lecanemab (more commonly known by its brand name, Leqembi) and donanemab (Kisunla), have been approved by the FDA, they have shown only mild to moderate success in slowing cognitive decline and are less effective in individuals with more advanced disease.
Researchers from Brigman and Women’s Hospital and Washington University in St. Louis investigated how xenon might impact the development of Alzheimer’s disease. Because of its effects as a general anesthetic, it is clear that the gas interacts with the central nervous system in some capacity and is known to cross the blood–brain barrier. However, the exact mechanism for this behavior is unclear.
Using mouse models for Alzheimer’s disease, the researchers found that xenon gas had a major effect on the microglia, the brain’s immune cells. Specifically, these cells adopted what the researchers termed the “pre-neurodegenerative microglia” or the “protective phenotype” state in response to xenon, in which microglia enhanced the clearing of amyloid plaques and reduced the swelling of neurons known as dystrophic neuritis, both of which are hallmarks of Alzheimer’s. Furthermore, xenon inhalation reduced brain atrophy—the loss of neurons and connections between them—and lowered the expression of inflammatory genes, which may have significant benefits for many degenerative neurological diseases if these results can be replicated safely in humans.
To test whether these cellular changes manifested in behavioral changes, the researchers subjected both mice receiving xenon, and those receiving regular air, to a nest building test, in which mice are evaluated on how well they shred material and incorporate it into a cohesive nest within a given amount of time as a test of normal functioning. Mice that inhaled xenon outperformed the control mice on this test.
The exact mechanism by which xenon exerts these brain benefits wasn’t a major part of the study and still remains unclear. It is useful as a general anesthetic because it blocks the N-methyl-D-aspartate (NMDA) receptor, preventing the neurotransmitter glutamate from binding and propagating nervous signals.4 Xenon has also been found to reduce post-surgical pain by regulating mitophagy, the breakdown of mitochondria, in microglia.5 Either or both of these mechanisms could be at play in xenon’s effect on Alzheimer’s progression.
Additionally, a 2019 study found that xenon inhalation in mouse models for traumatic brain injury led to a reduction in astrogliosis, the abnormal increase in the number of astrocytes (a type of glial cell) due to the destruction of neurons.6 The researchers saw a reduction in astrogliosis in the Alzheimer’s mice, suggesting that xenon may exert its effects across a range of neurological conditions.
It remains to be seen how xenon might improve the lives of Alzheimer’s patients. However, a phase 1 clinical trial of the treatment is expected to begin in healthy volunteers in early 2025, which may produce more insight into xenon’s potential benefits for the brain.
References
1. Franks, N. P., Dickinson, R., de Sousa, S. L. M., Hall, A. C. & Lieb, W. R. How does xenon produce anaesthesia? Nature 396, 324–324 (1998), DOI: 10.1038/24525
2. Brandao, W. et al. Inhaled xenon modulates microglia and ameliorates disease in mouse models of amyloidosis and tauopathy. Sci. Transl. Med. 17, eadk3690 (2025), DOI: 10.1126/scitranslmed.adk3690
3. ADI – Dementia statistics. https://www.alzint.org/about/dementia-facts-figures/dementia-statistics/.
4. Sanejouand, Y.-H. At least three xenon binding sites in the glycine binding domain of the N-methyl D-aspartate receptor. Arch. Biochem. Biophys. 724, 109265 (2022), DOI: 10.1016/j.abb.2022.109265
5. Lv, H. et al. Xenon ameliorates chronic post-surgical pain by regulating mitophagy in microglia and rats mediated by PINK1/Parkin pathway. PeerJ 12, e16855 (2024), 10.7717/peerj.16855
6. Campos-Pires, R. et al. Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury in mice. Br. J. Anaesth. 123, 60–73 (2019), 10.1016/j.bja.2019.02.032