This current sleeping pill can also protect your brain from Alzheimer’s disease

Lemborexant and similar sleep drugs show a potential for processing tau -related disorders, especially Alzheimer’s disease.

New research from the Washington University School of Medicine by St. Louis show that a commonly used sleep medication can restore normal sleep habits and protect mice from brain damage linked to neurodegenerative conditions such as Alzheimer’s disease. The medication, the mockery, blocks the accumulation of an abnormal form of the tau protein in the brain, thus reducing inflammation and cell lesions that the Tau generally causes in Alzheimer’s disease.

The results indicate that the Lemborexant, as well as other drugs which act similarly, could be promising to treat or prevent damage linked to the TAU in several neurodegenerative disorders, including Alzheimer’s disease, progressive supranuclear paralysis, cortico-obscur syndrome and certain forms of frontotemoral dementia.

The study was recently published in the journal Nature neuroscience.

Link the loss of sleep and the accumulation of tau

“We have long known that sleep loss is a risk factor for Alzheimer’s disease,” said main author David M. Holtzman, MD, Barbara Burton and Reuben M. Morriss III, professor of distinguished neurology at Washu Medicine. “In this new study, we have shown that the lemborexant improves sleep and reduces the abnormal tau, which seems to be a main engine of neurological damage that we see in Alzheimer’s disease and several related disorders. We hope that this observation will lead to other studies of this sleep drug and the development of new treatments available.

“The antibodies against the amyloid that we now use to treat patients with dementia in Alzheimer’s earlier and light are useful, but they do not slow down the disease as much as we want,” he added. “We need means to reduce the accumulation of abnormal tau and its accompaniment inflammation, and this type of sleeping pill deserves to be examined further. We are interested in continuing to both amyloid and tau with a combination of therapies could be more effective in slowing down or stopping the progression of this disease. ”

Testing the mouse models

Holtzman and his colleagues were among the first to demonstrate that a bad sleep is a risk factor for Alzheimer’s disease, closely linked to the accumulation of proteins such as the amyloid and the tau. In previous studies using genetically predisposed mice to develop these protein deposits, they have shown that the loss of sleep accelerates this accumulation. Their latest research has revealed that sleep improvement in these mice with lemborexant has reduced the tangles of Tau and lowered the level of death of nerve cells generally associated with Alzheimer’s disease.

Tau protein accumulates in the brain in several neurological disorders, including Alzheimer’s, where it triggers inflammation and degeneration of neurons. The Holtzman team, with Samira Parohizkar, PHD, as the first author, in part in part in the lemborexant because it targets the brain regions particularly vulnerable to an accumulation of abnormal tau. Above all, it does not interfere with motor coordination, a problem often raised when you consider sleep drugs for people with dementia.

Action mechanism and comparisons

The Lemborexant belongs to a class of three sleep drugs approved by the FDA which act as antagonists from the Orexine receptors. Orexins are small proteins that regulate sleep by binding to receptors on cell surfaces. By blocking the two types of orexin receptors (1 and 2), the lemborexant disturbs the activity of orexin, influencing the waking cycle and related processes such as the regulation of appetite.

The EISAI pharmaceutical company has provided lemborexant for these studies as part of research collaboration with Washu Medicine focused on the development of innovative treatments for Alzheimer’s disease, Parkinson’s disease and other neurodegenerative diseases.

In mice genetically subject to an accumulation of harmful tau, the Lemborexant has reduced brain lesions compared to witness mice. For example, those who receive the Lemborexant showed a volume of 30% to 40% larger in the hippocampus – part of the brain important to form memories – compared to witness mice and those which receive a different sleep drug, Zolpidem, which belongs to a different drug class. Zolpidem has increased sleep but had none of the protective effects against the accumulation of tau in the brain that has been observed with the Lemborexant, which suggests that the type of sleep assistance – Orexin receptor antagonist – is the key to the production of neuroprotective effects. The researchers also found that the beneficial effects were only observed in male mice, which they always work to understand.

The normal tau is important to maintain the structure and function of neurons. When he is in good health, he has a small number of chemical labels called phosphate groups. But when Tau takes over these chemical labels too much, it can group together, leading to an inflammation and the death of the nerve cells. The authors found that blocking orexin receptors, the lemborexant prevents excessive labels from being added to Tau, helping Tau to maintain its healthy roles in the brain.

Holtzman said that his team continued to explore the reasons why the neuroprotective effects of lemborexant treatment were only observed in male mice. He hypothesized that the sexual difference could be due to the observation that female mice having the same genetic predisposition to the accumulation of tau have developed a less severe neurodegeneration compared to male mice. With less damage to start, the potential beneficial effects of the drug could have been smaller and more difficult to detect.

Reference: “Lemborexant improves the loss and neurodegeneration of sleep mediated by the tau in men in a mouse of mouse of tauopathy” by Samira Parhizkar, Xin Bao, Wei Chen, Nicholas Rensing, Yun Chen, Michal Kipnis, Sihi Song, Grace Gent, Eric Tyssen, Melissa Manis, Choonghee Lue, Javin, Eric Tysen, Melissa Manis, Choonghee Lue, Javor Serrano, Megan E. Bosch, Emily Franke, Carla M. Yuede, Eric C. Landsness, Michael Wong and David M. Holtzman, May 27, 2025, Nature neuroscience.
Two: 10.1038 / S41593-025-01966-7

This work was supported by the National Health Institutes (NIH), P01NS074969 subsidy numbers, RF1NS090934 and RF1G061776; The JPB Foundation; the Alzheimer’s association, aarf-21-850865 subsidy number; The Rainwater Foundation and a Cobras Feldman scholarship.

Holtzman is an inventor of a patent authorized by the University of Washington with C2N diagnostics on the therapeutic use of anti-water antibodies. Holtzman has co -founded and is part of the scientific advisory council of C2N Diagnostics.

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