Xenon counteracts aspects of Alzheimer's

A noble undertaking...
17 January 2025

Interview with 

Oleg Butovsky, Harvard Brain Science Initiative

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Xenon treatment

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A new study has found that the noble gas xenon can counteract some of the major hallmarks of Alzheimer’s disease. Now this has only been demonstrated in mice engineered to develop an Alzheimer's-like pathology, as well as on cells grown in a culture dish, but it does look very interesting. Oleg Butovsky, at Harvard’s Brain Science Initiative, has found that exposure to xenon boosts the activity of the brain’s microglial cells. These are a bit like litter-pickers: they prowl around the brain clearing up rubbish. A burst of xenon gas seems to make them much more mobile so they can migrate towards mass more quickly, and they do a better clean up job in the process…

Oleg - The question was whether we can use xenon gas, which is a very rare gas in the atmosphere, to modulate immune cells of the brain in a way that would make them beneficial or reparative in Alzheimer's disease.

Chris - Why would a noble gas like xenon, A) get into the brain, and B) affect how cells in the brain work in the first place? What's the evidence that that's even possible?

Oleg - There's not much evidence, but historically, xenon has been tried for different things, including brain trauma and psychotic conditions—stuff like that. It is a very stable gas. It's actually been approved in Europe for use as anesthesia, although they don’t use it often because of the cost—it’s a very, very expensive and rare gas. But it can be used at particular dosages for anesthesia. That’s all.

Chris - Tell us about the study you did then in Alzheimer's disease. You're doing this in mice now. Mice don't naturally get Alzheimer's disease, so these must be mice that have been engineered in some way to develop something a bit like Alzheimer's.

Oleg - Yeah, that's absolutely right. These are transgenic mice that overexpress particular proteins called amyloids or tau proteins, which are pathogenic in Alzheimer's. In humans, as they age, these proteins start to aggregate and become toxic. This is how it’s done in the mice—they overexpress and have high levels of human proteins, leading them to develop signs of pathology resembling those seen in human Alzheimer’s brains.
Although, before moving to the mice, we did some simple experiments to see whether xenon had any effect related to neurodegenerative conditions. My lab, many years ago, developed an interesting experimental paradigm where we transplant a cell into a living mouse brain. Within this environment, immune cells called microglia migrate toward the transplanted cells. They recognise dying cells, migrate to them, and phagocytose them. This is a great way to test many things, including xenon.
Mice were exposed to xenon inhalation for about 40 minutes. Microglia were affected in a way that made them very quickly migrate, recognise these dying cells, and phagocytose them. This was the trigger for us to move forward and try xenon inhalation in Alzheimer’s mouse models. The microglia became more migratory and more phagocytic.

Chris - And what impact did that enhanced activity conferred on the microglia by the xenon treatment have on the progression or presentation of Alzheimer’s in these mice?

Oleg - So, we started by looking at whether we could see a reduction in amyloid plaques, and this is what we found. In addition, there was an associated reduction of so-called neuritic plaques. These aggregates are what lead to neuronal death and synaptic loss. We also found that xenon mitigates this pathological evidence.
As we move forward, we’d like to see if xenon has an effect on cognitive improvements. That’s going to be very important for its potential use as a treatment for Alzheimer’s.

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