Your sleep may be hiding an early clue to Alzheimer’s

 Could subtle changes during sleep reveal vulnerability to Alzheimer's disease years before memory problems become noticeable? Researchers at ULiège, supported by the Stop Alzheimer's Foundation, are investigating whether the sleeping brain may contain early clues.

Scientists from the University of Liège (GIGA Neurosciences) examined sleep patterns in more than 500 healthy people. Among participants in middle age, more frequent nighttime micro awakenings were associated with a higher genetic risk of developing Alzheimer's disease. That relationship was not detected among younger adults.

The findings, published in the journal Sleep, raise the possibility that sleep measurements could eventually help researchers identify people who may be more vulnerable to Alzheimer's before symptoms develop.

Looking for Alzheimer's Clues Before Symptoms

Researchers have spent years investigating connections between disturbed sleep and neurodegenerative diseases. The University of Liège study adds another piece to that research by suggesting that the relationship between sleep and Alzheimer's risk may begin well before recognizable symptoms emerge.

Because genetics play a partial role in Alzheimer's disease (Alzheimer's disease is neither purely hereditary nor entirely independent of genes), the researchers calculated a polygenic risk (i.e., summarizing the combined influence of your genes on your probability of developing a given disease in a single figure) for more than 500 healthy participants.

Most were young adults (aged 18 to 31), while the study also included an older group (aged 50 to 69). Importantly, the polygenic risk measured in the study remained low and cannot determine whether any particular person will eventually develop Alzheimer's disease.

The researchers then compared these genetic risk estimates with different characteristics of each participant's sleep.

Tiny Awakenings During the Night

The analysis revealed an association between genetic risk for Alzheimer's disease and the frequency of nighttime micro awakenings. These are very brief bursts of brain activity that can interrupt the normal sleep cycle without causing someone to become fully awake.

Among the younger participants, researchers found no connection between these micro awakenings and Alzheimer's genetic risk. A different pattern appeared in the older group. Participants who experienced more frequent micro awakenings also tended to have higher genetic risk, despite being healthy, relatively young and free of Alzheimer's symptoms.

"These micro-awakenings are therefore not insignificant," emphasizes Puneet Talwar, a researcher at the GIGA ULiège laboratory, "certain profiles could promote the accumulation of proteins involved in Alzheimer's disease and be associated with increased vulnerability."

A Tiny Brain Region Draws Attention

The researchers also examined the locus coeruleus, a tiny area deep within the brainstem that is roughly the size of a grain of rice. It plays an important role in regulating wakefulness, attention, and sleep.

"This region is difficult to observe, but it appears to play a role in the early mechanisms linked to the disease," explains Gilles Vandewalle, co-director of the GIGA CRC In Vivo Imaging technology platform and Fund for Scientific Research - FNRS Research Director at ULiège.

In 2025, a preliminary study carried out with the 7-Tesla MRI scanner at the ULiège platform allowed the team to examine the locus coeruleus in greater detail. The researchers found that characteristics of sleep quality (speed of falling asleep, depth) were associated with the condition of the brainstem beginning at a young age.

They also found that healthy functioning of the locus coeruleus was related to the quality of REM sleep, a stage of sleep that plays an important role in memory.

The locus coeruleus is especially interesting to Alzheimer's researchers because it is among the earliest brain regions where abnormal protein deposits can appear. Such deposits may begin accumulating as early as adolescence, although scientists still do not fully understand what these early changes mean.

Could Sleep Become an Early Alzheimer's Marker?

Taken together, the findings point toward possible new approaches for Alzheimer's screening and prevention. In the future, analyzing sleep could potentially complement other methods for identifying people who may be vulnerable to the disease before symptoms become apparent.

"Sleep could become an accessible marker for the early identification of vulnerable individuals," adds Gilles Vandewalle.

Researchers are also interested in whether improving sleep could eventually help prevent or slow disease progression among people with a genetic predisposition to Alzheimer's.

"This research shows that sleep is not only an indicator of health, but also a potential lever for intervention," adds Lucie Leroux, head of French-speaking activities at the Stop Alzheimer's Foundation.

More than 220,000 people in Belgium are affected by Alzheimer's disease. For now, however, the new findings show statistical associations rather than proof that particular sleep patterns cause or predict the disease. Additional research will be needed to confirm the results, and the findings cannot currently be used to determine whether an individual will develop Alzheimer's.

Even so, the research provides another glimpse into changes that may occur long before Alzheimer's becomes clinically visible and underscores the value of basic research aimed at understanding and, eventually, anticipating the disease.

Journal Reference:

1. Nasrin Mortazavi, Puneet Talwar, Ekaterina Koshmanova, Roya Sharifpour, Elise Beckers, Alexandre Berger, Islay Campbell, Ilenia Paparella, Fermin Balda, Ismael Dardour Hamzaoui, Christian Berthomier, Christine Bastin, Christophe Phillips, Pierre Maquet, Fabienne Collette, Mikhail Zubkov, Laurent Lamalle, Gilles Vandewalle. REM sleep quality is associated with balanced tonic activity of the locus coeruleus during wakefulness. Journal of Biomedical Science, 2025; 32 (1) DOI: 10.1186/s12929-025-01127-9

Courtesy:

University of Liège. "Your sleep may be hiding an early clue to Alzheimer’s." ScienceDaily. ScienceDaily, 28 August 2026. <www.sciencedaily.com/releases/2026/08/260828005218.htm>. 

 

 

 

 

 

 

A cancer therapy put severe rheumatoid arthritis into remission

 Immunotherapies such as CAR T-cell therapy were originally developed mainly to fight cancer. But scientists are now investigating whether these personalized treatments, made from a patient's own immune cells, could also help treat or even potentially cure autoimmune diseases.

Researchers at Charité - Universitätsmedizin Berlin have now tested CAR T-cell therapy in six people with particularly severe rheumatoid arthritis. The world's first clinical trial of its kind, reported in Nature Medicine, produced encouraging early results. Disease activity fell substantially in every participant, and by the end of the observation period, three patients no longer needed rheumatoid arthritis medication.

Why Rheumatoid Arthritis Can Be So Difficult To Treat

Rheumatoid arthritis is a chronic autoimmune disease in which the immune system mistakenly attacks the joints. Repeated inflammation causes swelling and can eventually damage the joints.

Existing medications are often effective at controlling inflammation, but they generally do not cure the disease. As a result, many patients need lifelong treatment with anti-inflammatory drugs and medications that suppress the immune system, which can also cause side effects.

For some people, even newer therapies do not work well enough. Doctors describe these cases as treatment-refractory rheumatoid arthritis. Patients can continue to experience pain, limited mobility, and major reductions in quality of life despite trying multiple treatments.

"One reason could be disease-driving B cells - memory cells of the adaptive immune system that may survive in the lymph nodes, bone marrow or joint tissue after an infection, where they produce harmful antibodies directed against the body's own tissues and repeatedly reignite the inflammation," explains Prof. David Simon, who designed the trial for this patient group together with Prof. Gerhard Krönke at Charité's Department of Rheumatology and Clinical Immunology.

The researchers are testing whether CAR T cells can seek out these disease-driving B cells even when they are buried deep within body tissues. Their goal is to eliminate as much of the abnormal B-cell memory as possible and effectively give the B-cell system a new start.

Using Cancer Immunotherapy To Reset the Immune System

CAR T cells were first developed as a cancer treatment, but their potential uses are expanding. In cancer therapy, a patient's immune cells are modified so they can recognize and destroy tumor cells. For autoimmune diseases, scientists instead want to direct those engineered cells toward immune cells that help sustain the disease.

"The identifying marker on many B cells, both abnormal B cells in cancers of the blood or lymphatic system and disease-driving B cells in rheumatoid arthritis, is the surface molecule CD19. You could think of it as a kind of 'name tag'," explains David Simon. "To enable CAR T cells to detect and eliminate the disease-causing cells, we equip patients' own immune cells with a receptor that acts like a search sensor for CD19."

To produce this form of CD19 CAR T-cell therapy, doctors first collect T cells from the patient's blood. T cells are immune cells that normally help recognize and destroy infected or abnormal cells.

Scientists then genetically modify those T cells in the laboratory. The cells receive a chimeric, or artificial, antigen receptor known as a CAR, which is designed to bind specifically to CD19.

Before receiving the modified cells, patients undergo a short course of preparatory chemotherapy. This temporarily lowers the number of certain immune cells, creating room for the CAR T cells to multiply and function effectively.

The engineered cells are then returned to the patient in a single infusion. Once inside the body, they search for cells carrying CD19 and attack them. This temporarily removes all CD19-positive B cells, including long-lived disease-driving cells in the joints that can otherwise be difficult to reach. By clearing out those cells, the treatment may allow the immune system to reset.

First Trial in Severe Rheumatoid Arthritis

For the first clinical trial evaluating both the safety and effectiveness of CD19 CAR T-cell therapy in rheumatoid arthritis, the Charité team initially enrolled six patients with especially severe disease.

The group included three women and three men between the ages of 31 and 69. During the previous decade, they had received as many as eight targeted or biologic therapies, but none had controlled their disease adequately.

Researchers wanted to learn whether CAR T cells could reach the disease-driving B cells inside the joints and whether the approach could do so safely.

The first phase of the COMPARE trial produced results the team considers highly encouraging.

"Disease activity decreased markedly in all six patients. During follow-up of up to one year, three patients were in sustained remission without any medication for rheumatoid arthritis," reports Gerhard Krönke, who leads the joint Clinical Rheumatology research group at Charité and the German Rheumatology Research Center (DRFZ), a Leibniz Institute. "This is particularly remarkable given that none of the established treatments had previously been able to relieve their symptoms adequately."

CAR T Cells Reached Hidden Disease Reservoirs

The treatment appeared to do more than temporarily reduce inflammation in the joints. Researchers found that the modified immune cells also reached and eliminated disease-promoting B cells in deeper locations, including the bone marrow, lymph nodes, and joint tissue.

During regular follow-up visits over the following 12 months, levels of the autoantibodies associated with rheumatoid arthritis dropped sharply.

David Simon adds: "When the B-cell system later recovered, predominantly naïve B cells that had not yet been shaped by the disease returned. In contrast, the B cells directed against the body's own tissues that had been present before treatment were no longer detectable in almost all patients, an indication that the treatment may indeed be able to reset the pathological immune memory."

Importantly, antibodies generated by earlier vaccinations, including those against chickenpox and tetanus, could still be detected. That suggests protective antibody memory was largely preserved even though the therapy caused a profound temporary depletion of B cells.

Researchers still need to determine whether the therapy has any longer-term effects on the immune system.

Promising Results, but the Therapy Remains Experimental

The trial suggests that a single CAR T-cell treatment can, in some patients, produce a sustained period without symptoms or rheumatoid arthritis medication. This state of disease inactivity is known as remission.

For carefully selected patients whose rheumatoid arthritis does not respond adequately to available treatments, researchers hope it may eventually be possible to directly reset pathological immune memory and stop the ongoing inflammation rather than continuously suppressing it with medication.

However, CAR T-cell therapy for autoimmune diseases, including rheumatoid arthritis, is still experimental. Researchers do not yet have long-term experience with the treatment.

Responses also differed among the six participants. Some did not achieve a complete response, and one patient's disease returned after an initial period of medication-free remission.

So far, however, the researchers consider the safety findings encouraging.

"After the participants received the CD19 CAR T cells, we observed only a temporary, mild-to-moderate cytokine release syndrome (CRS) in all participants, which was readily manageable. There were no severe neurological complications or other serious adverse events, and infections were rare," explains Dr. Marie Luise Hütter-Krönke, Medical Director of the Hematology Early Clinical Trial Unit at Charité's Department of Hematology, Oncology and Cancer Immunology.

A Larger Comparison Is Next

The second phase of the trial will include ten additional patients. Researchers plan to compare CAR T-cell therapy with an already approved rheumatoid arthritis drug that also targets B cells.

The comparison should help determine whether CAR T cells produce stronger or longer-lasting effects and whether they truly reset immune memory.

If these results are confirmed in this phase and in future larger studies, CAR T-cell therapy could eventually offer another option for people with severe rheumatoid arthritis whose lives are significantly affected by the disease and who currently have no adequate treatment.

About the Study

The first of the two phases of the COMPARE study was designed to assess the safety and effectiveness of CD19 CAR T-cell therapy in treatment-refractory rheumatoid arthritis.

Major contributors included researchers from Charité's Department of Rheumatology and Clinical Immunology and the Department of Hematology, Oncology and Cancer Immunology at Campus Benjamin Franklin, along with scientists from the Cluster of Excellence ImmunoPreCept, the German Rheumatology Research Center (DRFZ), a Leibniz Institute, and the Fraunhofer Institute for Translational Medicine and Pharmacology ITMP.

The study was initiated and designed at Charité and also received support from Kyverna Therapeutics. The immunotherapy company had no role in designing the study, collecting or analyzing the data, or presenting the results.

Journal Reference:

1. Fredrik N. Albach, Marie C. Rehm, Marie Luise Hütter-Krönke, Thanh Hang Le, Julia M. Giezen, Murat Torgutalp, Arne Sattler, Ioanna Minopoulou, Robert Biesen, Edgar Wiebe, Vincent Casteleyn, Thorben Witte, Christian Furth, Jan Zernicke, Melanie Nuesch Germano, Johan Verhagen, Artur Wilhelm, Maria Dzamukova, Klaus Engel, Simon Schallenberg, Aimo Kannt, Nicole Ziegler, Michaela Fehringer, Udo Schneider, Nadine Unterwalder, Mark Beling, Alexander Pfeil, Elpida Phithak, Martin Krusche, Olaf Penack, Tobias Alexander, Werner Stenzel, Manfred Wuhrer, Kamran Movassaghi, Thomas Dörner, Eicke Latz, Thomas Vogl, Antonia Busse, Georg Schett, Hans Ulrich Scherer, Rene E. M. Toes, Arnd Kleyer, Ulrich Keller, Lars Bullinger, David Simon, Gerhard Krönke. CD19 CAR T cell therapy for treatment-refractory seropositive rheumatoid arthritis: a phase 1 trial. Nature Medicine, 2026; DOI: 10.1038/s41591-026-04603-3

Courtesy:

Charité - Universitätsmedizin Berlin. "A cancer therapy put severe rheumatoid arthritis into remission." ScienceDaily. ScienceDaily, 29 August 2026. <www.sciencedaily.com/releases/2026/08/260828082330.htm>.