Promising Breakthrough: Common Sleeping Pill May Slow Alzheimer’s Progression

Exciting news on the Alzheimer’s research front! A drug commonly used to treat insomnia, lemborexant, has shown remarkable potential in preclinical trials by slowing the buildup of abnormal proteins associated with neurodegenerative diseases like Alzheimer’s. This discovery could pave the way for new strategies to combat cognitive decline.

The Growing Challenge of Dementia

With nearly 10 million new cases of dementia globally each year, the search for effective treatments is more urgent than ever. Despite decades of dedicated research, there are still very few options that offer clear benefits to those affected by these devastating conditions.

Connecting Sleep and Alzheimer’s

Recognizing the established links between poor sleep and Alzheimer’s, a team of neurologists led by Samira Parhizkar and David Holtzman at Washington University investigated lemborexant. This central nervous system depressant was approved by the FDA in December 2019 as a sleep aid.

“We have shown that lemborexant improves sleep and reduces abnormal tau, which appears to be a main driver of the neurological damage that we see in Alzheimer’s and several related disorders,” explains Dr. Holtzman.

Targeting Tau Proteins

While much attention has been given to amyloid beta proteins in Alzheimer’s, tau proteins are also crucial. Normally, tau proteins help structure brain cells. However, abnormal tau proteins have been linked to the rate of brain atrophy in animal models of the disease.

“The antibodies to amyloid that we now use to treat patients with early, mild Alzheimer’s dementia are helpful, but they don’t slow the disease down as much as we would like,” says Dr. Holtzman. “We need ways to reduce the abnormal tau buildup and its accompanying inflammation, and this type of sleep aid is worth looking at further.”

Unexpected Findings

The researchers compared lemborexant with another common sleep aid, zolpidem. Surprisingly, mice treated with lemborexant retained up to 40% more volume in their hippocampus (the brain’s memory-forming region) compared to those given zolpidem or no sleep aid at all.

“What was surprising was that these effects were not seen with a standard sleep drug like zolpidem, which increases NREM sleep similarly to lemborexant,” Parhizkar noted. “This suggests that the benefit is not just about more sleep, but rather how that sleep is promoted.”

The key seems to lie in how the two drugs work. Lemborexant blocks orexin, a neuropeptide that regulates the sleep cycle. The team found that genetically modifying mice to lack orexin receptor 2 also reduced tau buildup in their brains, supporting the idea that this mechanism is important.

Important Next Steps

While these findings are exciting, there are some important considerations:

• Gender-Specific Results: The protective effects of lemborexant were observed only in male mice, even though female mice were also tested. This is an area that requires further investigation.
• Translating to Humans: Results from mouse studies don’t always directly translate to humans.
• Long-Term Use: Lemborexant is currently approved for short-term use in humans, so its long-term impacts and effectiveness in reducing tau in people still need to be studied.

Despite these questions, the potential for an existing, FDA-approved drug to impact Alzheimer’s progression is incredibly promising. Researchers hope that if these results hold true in human trials, early intervention with a drug like lemborexant could potentially delay the onset and progression of neurodegeneration.

Parhizkar, S., Bao, X., Chen, W. et al. Lemborexant ameliorates tau-mediated sleep loss and neurodegeneration in males in a mouse model of tauopathy. Nat Neurosci (2025). https://doi.org/10.1038/s41593-025-01966-7