Many of the existing studies on Alzheimer’s disease have focused on the amyloid plaques and tau tangles found in the brains of patients with the condition. But a rising body of research focuses on one potential cause of those plaques and tangles: inflammation.

Inflammation is believed to contribute to the growth of amyloid plaques by stimulating the production of microglia in the brain. These specialized white blood cells attack amyloid plaque as if they were an infection. Unfortunately, amyloid plaque is persistent and doesn’t clear out immediately.

During this standoff, inflammatory cells called cytokines are produced, which cause oxidative stress and harm healthy brain tissue. They also may increase the enzyme BACE1, which is thought to stimulate amyloid production while weakening the microglia’s ability to eliminate it.

So, could controlling runaway inflammation prevent Alzheimer’s? Researchers are getting closer to finding out, and identifying some unusual potential treatments in the process…

Breathe in the protective power of xenon

In a study by researchers at Mass General Brigham and Washington University School of Medicine in St. Louis, mouse models of Alzheimer’s disease were treated with xenon gas. This gas is used in human medicine as an anesthetic and neuroprotectant for treating brain injuries. Xenon gas can penetrate the blood-brain barrier, passing from the bloodstream directly into the fluid surrounding the brain.

The results were amazing. The Alzheimer’s mice that inhaled xenon gas showed reduced brain atrophy and neuroinflammation and improved nest-building behaviors. The gas also triggered and increased a protective microglial response associated with clearing amyloid and enhancing cognition.

The findings underscore the promising potential of xenon as a therapeutic, instilling hope and optimism. The results are robust enough to support the initiation of a Phase I clinical trial of xenon gas in healthy volunteers in early 2025.

“It is a very novel discovery showing that simply inhaling an inert gas can have such a profound neuroprotective effect,” says senior and co-corresponding author Dr. Oleg Butovsky of the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital (BWH).

“One of the main limitations in the field of Alzheimer’s disease research and treatment is that it is extremely difficult to design medications that can pass the blood-brain barrier — but Xenon gas does,” Butovsky says. “We look forward to seeing this novel approach tested in humans.”

Protection extended to amyloid and tau

Dr. David M. Holtzman from Washington University School of Medicine in St. Louis notes that two types of Alzheimer’s mouse models were used: one focused on amyloid and one focused on tau.

“It is exciting that in both animal models that model different aspects of Alzheimer’s disease, amyloid pathology in one model and tau pathology in another model, that xenon had protective effects in both situations,” Holtzman says.

Microglial dysfunction is a hallmark of Alzheimer’s. Butovsky’s lab previously confirmed a specific phenotype of microglia can be modulated in a way that is protective in Alzheimer’s.

The early phases of the clinical trial in humans will establish safety and dosage. At the same time, the researchers plan to continue studying the mechanisms by which xenon gas achieves its effects. They also will examine its potential for treating other diseases such as multiple sclerosis, amyotrophic lateral sclerosis and eye diseases that involve the loss of neurons.

The team is also working on technologies to make xenon gas use more efficient as well as potentially recycle it.

“If the clinical trial goes well, the opportunities for the use of xenon gas are great,” says co-author Dr. Howard Weiner, co-director of the Ann Romney Center for Neurologic Diseases at BWH and principal investigator of the upcoming clinical trial. “It could open the door to new treatments for helping patients with neurologic diseases.”

As exciting as this breakthrough is, it will be years before it results in a treatment. Until then, your best bet for reducing the odds of developing Alzheimer’s is eating right, exercising and taking advantage of nootropics that help protect against cognitive decline and douse the fires of inflammation.

Sources:

Study finding Xenon gas could protect against Alzheimer’s disease leads to start of clinical trial — EurekAlert!

Inhaled xenon modulates microglia and ameliorates disease in mouse models of amyloidosis and tauopathy — Science Translational Medicine