In a new study entitled “Rescue of long-range circuit dysfunction in Alzheimer’s disease models,” researchers discovered why Alzheimer’s disease patients experience sleep disturbances and discovered potential therapeutics to counteract this effect. The team observed that improving sleep in mouse models of Alzheimer’s disease also benefits their memory performance. The study was published in the journal Nature Neuroscience.
Alzheimer’s disease patients may experience sleep disturbances, a condition that often precedes Alzheimer’s more characteristic symptoms, such as memory impairment. It is well established that sleep is a crucial event in memory formation since it is then that our brain generates sleep waves, known as slow oscillations, which play a key role not only in consolidating what we learned during the day, but also in forming long-term memories. The waves are generated in the brains’ cortex through a network of nerve cells and propagate to through the brain, reaching other brain areas, such as the hippocampus.
Dr. Marc Aurel Busche, scientist at the Department of Psychiatry and Psychotherapy at TUM University Hospital Klinikum rechts der Isar and TUM Institute of Neuroscience noted in a press release, “These waves are a kind of signal through which these areas of the brain send mutual confirmation to say ‘I am ready, the exchange of information can go ahead’. Therefore, there is a high degree of coherence between very distant nerve cell networks during sleep.”
The team directed by Dr. Busche and Prof. Dr. Arthur Konnerth from the Institute of Neuroscience, used mouse models that recapitulate the human’s features of Alzheimer’s disease, namely the accumulation of β-amyloid plaques in patients’ brains. The team discovered that accumulation of these plaques interferes with brains’ slow oscillations. Specifically, “The slow oscillations do still occur, but they are no longer able to spread properly – as a result, the signal for the information cross-check is absent in the corresponding regions of the brain,” explained Dr. Busche.
The results also showed that a balance in excitatory and inhibitory signs is key for slow oscillations to spread effectively through the brain, and that this balance is perturbed in Alzheimer’s disease via deposition of protein β-amyloid aggregates. When scientists administered very low doses of sleep-inducing drugs, such as benzodiazepines (administered with a dose 10 times lower than the standard dose) in mice, sleep waves effectively spread again, leading to improvements in the animals’ learning performance.
Dr Busche explained the significance of the study, “These findings are of great interest for two reasons: firstly, mice and humans have the same sleep oscillations in the brain – the results are thus transferrable. Secondly, these waves can be recorded with a standard EEG monitor, so that any impairment may also be diagnosed at an early stage.”