Could subtle changes during sleep reveal a susceptibility to Alzheimer’s disease, even years before memory problems become noticeable? Researchers at the University of Liège (ULiège), with support from the “Stop Alzheimer’s Foundation,” are investigating whether the sleeping brain might provide early clues.

Scientists at the University of Liège (GIGA Neurosciences) examined the sleep patterns of more than 500 healthy people. Among middle-aged participants, more frequent nighttime micro-awakenings were associated with a higher genetic risk of developing Alzheimer’s. This association was not observed in younger adults. The results, published in the journal Sleep, suggest that sleep measurements could ultimately help researchers identify people who may be more susceptible to Alzheimer’s even before symptoms appear.

Searching for Signs of Alzheimer’s Before Symptoms Appear

Researchers have been investigating links between sleep disorders and neurodegenerative diseases for years. The study from the University of Liège contributes further to this research by suggesting that the link between sleep and Alzheimer’s risk may exist long before recognizable symptoms appear.

Since genetics plays a certain role in Alzheimer’s disease (Alzheimer’s is neither purely hereditary nor completely independent of genes), the researchers calculated a polygenic risk (i.e., the combined influence of genes on the probability of developing a specific disease, summarized as a single number) 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). It is important to note that the polygenic risk measured in the study remained low and cannot predict whether a specific person will ultimately develop Alzheimer’s disease. The researchers then compared these genetic risk estimates with various sleep characteristics of the individual participants.

A Tiny Brain Region Takes Center Stage

The analysis revealed a link between the genetic risk for Alzheimer’s and the frequency of nocturnal micro-awakenings. These are very brief periods of increased brain activity that can interrupt the normal sleep cycle without the person fully waking up.

Among the younger participants, the researchers found no association between these micro-awakenings and genetic risk for Alzheimer’s. A different pattern emerged in the older group. Participants who experienced more frequent micro-awakenings also tended to have a higher genetic risk, even though they were healthy, relatively young, and free of Alzheimer’s symptoms. “These micro-awakenings are therefore not insignificant,” emphasized Puneet Talwar, a researcher at the GIGA-ULiège laboratory. “Certain patterns could promote the accumulation of proteins involved in Alzheimer’s disease and be associated with increased susceptibility.” The researchers also examined the locus coeruleus, a tiny area deep within the brainstem that is about the size of a grain of rice. Despite its small size, it performs important functions: Among other things, it is involved in regulating wakefulness, attention, and sleep, and influences how the brain responds to environmental stimuli.

This region is of particular interest for Alzheimer’s research. The locus coeruleus is one of the brain regions where pathological changes may appear very early on—long before typical symptoms such as memory problems occur. These include, among other things, deposits of the tau protein, which plays an important role in Alzheimer’s disease. Such early changes may potentially impair the function of the locus coeruleus and thus also affect processes related to sleep and wakefulness. “This region is difficult to observe, but it appears to play a role in the early mechanisms associated with the disease,” explains Gilles Vandewalle, co-director of the GIGA-CRC “In Vivo Imaging” technology platform and research director of the Belgian Fund for Scientific Research (FNRS) at ULiège.

A preliminary study by the team from 2025 had already shown just how closely this small brain region might be linked to sleep. Using a high-resolution 7-Tesla MRI scanner, the researchers examined the locus coeruleus in greater detail. In doing so, they found evidence that certain characteristics of sleep quality are already linked to the condition of this brain region in young adults. These included, among other things, the time it takes to fall asleep and sleep depth.

Is there a Cause-and-Effect Relationship?

In addition, the scientists identified a link between the function of the locus coeruleus and the quality of REM sleep. During this sleep phase, the brain is particularly active. It is associated, among other things, with the processing and consolidation of memories. Changes in REM sleep could therefore potentially affect processes that are important for memory function. What is particularly intriguing is that changes in the locus coeruleus can apparently begin very early in life. Abnormal protein deposits have been observed in this region, in some cases even in young people.

However, it is not yet clear exactly what these early deposits mean or whether they actually herald a later disease process. For the researchers, this suggests a possible interplay: changes in the locus coeruleus could influence sleep, while altered sleep, in turn, could be linked to further changes in the brain. Future studies will need to determine whether a cause-and-effect relationship exists or whether the two processes are merely interconnected.

Could Sleep Become an Early Marker for Alzheimer’s?

The findings raise an intriguing question: Could sleep one day help identify an increased risk of Alzheimer’s even before the first memory problems or other typical symptoms appear? Sleep can be studied relatively easily and noninvasively. As a result, it could potentially complement other methods used to detect early changes in the brain. “Sleep could become an easily accessible marker for the early identification of susceptible individuals,” said Gilles Vandewalle. However, there is still a long way to go before that becomes a reality. The current findings merely show a statistical association between certain sleep characteristics and a higher genetic risk for Alzheimer’s. They do not show that frequent micro-awakenings cause Alzheimer’s disease or that sleep patterns can reliably predict who will develop the disease later in life.

The question of whether better sleep can actually influence the risk of Alzheimer’s also remains open. The researchers therefore want to investigate whether changes in sleep are not only an indication of early processes in the brain, but also whether a targeted improvement in sleep quality could influence these processes. “This research shows that sleep is not only an indicator of health, but also a potential starting point for interventions,” said Lucie Leroux of the “Stop Alzheimer’s” Foundation. However, further—and, above all, long-term—studies are necessary. They must show whether the observed correlations persist over time and whether changes in sleep can indeed be linked to later changes in the brain or the onset of Alzheimer’s symptoms.

The current study therefore does not yet provide a new Alzheimer’s test. However, it does show that changes in sleep related to the disease’s biological processes may already be observable at an early stage. Should this association be confirmed in further studies, sleep analysis could in the future help identify at-risk individuals earlier and provide a more precise understanding of how Alzheimer’s develops long before the first symptoms appear. This means that sleep could become relevant not only for early detection. The research also raises the question of whether specifically improving sleep quality might help influence disease-related changes. Further research will have to show whether this actually leads to new possibilities for the prevention or treatment of Alzheimer’s.