Sleep modulation in mice with Alzheimer’s and Parkinson’s disease

Alzheimer’s and Parkinson’s disease are brain disorders often accompanied by sleep-wake disturbances. Research suggests that modulating deep sleep could influence the neuropathological progression of both diseases. Daniela Noain and her team from the University Hospital Zurich tested a novel method to modulate deep sleep and explored its impact on Alzheimer’s and Parkinson’s disease mice.

There are few pharmacological treatments available to deepen sleep. These interventions are often burdensome and have limitations such as build-up of dependency or tolerance. Thus, the research group tested an alternative non-invasive method to deepen sleep without drastically changing its general structure. It is called mouse closed-loop auditory stimulation (mCLAS) and consists of 15-millisecond noise clicks played to mice during particular sleep phases. In previous studies, the group demonstrated that mCLAS influences brain activity during sleep in healthy animals. Now, Noain’s team investigated whether they could specifically deepen sleep in Alzheimer’s and Parkinson’s disease and thus potentially impact underlying neurodegeneration.

To do this, the researchers used genetically modified mice that will later develop either Alzheimer’s or Parkinson’s disease alongside siblings without genetic mutations. Both Alzheimer’s and Parkinson’s disease mice were examined at an early stage of the disease. They already show brain pathology and sleep-wake disturbances at that stage but suffer from no or very mild motor or cognitive symptoms. The goal was to determine whether mCLAS could have a beneficial effect at this early stage and, thus, perhaps arrest or slow disease progression.

The study revealed that the sounds presented to the mice during deep sleep successfully enhanced sleep quality and depth in Alzheimer’s and Parkinson’s disease mice. In addition, the group has collected preliminary evidence that deepening sleep also exerts a reduction of pathological brain findings that are associated with Alzheimer’s or Parkinson’s diseases. This suggests that the method could slow down the progression of both disorders. Further research is ongoing in the group to understand the potential of long-term mCLAS implementation and to explore the feasibility and effectiveness of this non-invasive sleep-based therapy for neurodegenerative diseases, both in mice and humans.

Reference: Dias, I., Baumann, C.R., Noain, D.: mCLAS adaptively rescues disease-specific sleep and wake phenotypes in neurodegeneration. Sleep Medicine, Volume 124, 704-716, 2024 https://doi.org/10.1016/j.sleep.2024.11.009

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