Could subtle signs of the disease appear during sleep long before the first memory problems emerge? Researchers are investigating this possibility with support from the Stop Alzheimer’s Foundation.
The earliest signs of Alzheimer’s vulnerability may emerge during sleep, years before memory problems become apparent. Researchers at ULiège, supported by the Stop Alzheimer’s Foundation, are investigating whether subtle changes in sleep could provide clues to disease risk long before clinical symptoms develop.
Scientists at the University of Liège (GIGA Neurosciences) analyzed sleep patterns in more than 500 healthy people. Among middle-aged participants, more frequent nocturnal micro-awakenings were associated with greater genetic risk of Alzheimer’s disease, an association that did not appear in young adults. Published in Sleep, the findings suggest that monitoring sleep could eventually contribute to identifying people who may be more vulnerable to the disease.
Researchers have spent years examining connections between disturbed sleep and neurodegenerative diseases, but the University of Liège work suggests that such relationships could emerge before symptoms become visible.
To investigate, the researchers took advantage of the fact that Alzheimer’s has a genetic component (Alzheimer’s disease is neither purely hereditary nor entirely independent of genes) and calculated 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), although the study also included people (aged 50 to 69). The researchers stress that this polygenic risk remains low and cannot determine who will eventually develop Alzheimer’s. They then compared these risk estimates with characteristics of each participant’s sleep.
Micro awakenings track genetic risk
The clearest association involved nocturnal micro-awakenings, short bursts of brain activity that can interrupt the sleep cycle without fully waking a person. No relationship with genetic Alzheimer’s risk appeared among the younger participants. In the older group, however, people with more frequent micro-awakenings tended to have higher genetic risk despite remaining relatively young and showing no signs of the disease.
“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.”
Another focus was the coeruleus locus, a brainstem region about the size of a grain of rice that contributes to wakefulness, attention, and sleep regulation.
“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 a preliminary 2025 study, researchers used the 7-Tesla MRI scanner at the ULiège platform to analyze the locus coeruleus in detail.
They found that sleep quality (speed of falling asleep, depth) was related to the condition of the brainstem from a young age and that proper functioning of the locus coeruleus depended on the quality of REM sleep, a sleep stage important for memory. The region is particularly relevant because it is among the first places where abnormal protein deposits appear, sometimes beginning in adolescence, although scientists do not yet fully understand what those early deposits mean.
Sleep could become an early marker
Taken together, the observations suggest possible new directions for screening and prevention. Sleep measurements might eventually supplement other methods for identifying vulnerable people before symptoms emerge.
“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 help prevent or slow disease progression among genetically predisposed people. “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.
Alzheimer’s disease affects more than 220,000 people in Belgium, but the researchers caution that these results represent statistical associations that still need confirmation and cannot currently predict whether an individual will develop the disease. Even so, the findings provide another avenue for understanding how Alzheimer’s may begin and, eventually, how researchers might identify vulnerability earlier.
Reference: “REM sleep quality is associated with balanced tonic activity of the locus coeruleus during wakefulness” by 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 and Gilles Vandewalle, 11 March 2025, Journal of Biomedical Science.
DOI: 10.1186/s12929-025-01127-9
This work was supported by Fonds National de la Recherche Scientifique (FRS-FNRS, T.0242.19, T.0238.23 and J. 0222.20), Action de Recherche Concertée—Fédération Wallonie-Bruxelles (ARC SLEEPDEM 17/27-09), Fondation Recherche Alzheimer (SAO-FRA 2019/0025 & 2022/0014), Fondation Léon Fredericq, ULiège, European Regional Development Fund (Radiomed, Biomed-Hub, WALBIOIMAGING).
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