Researchers from the Technical University of Munich (TUM) have shown that protein deposits in the brains of Alzheimer’s patients, known as beta-amyloid plaques, disturb memory formation during sleep. The results are published in Nature Neuroscience.
In “normal” sleeping brains, slow waves, known as slow oscillations, help consolidate what has been learned and shifts memories into long-term storage. The waves are formed in the brain’s cortex through a network of nerve cells, and are then spread out into other parts of the brain such as the hippocampus.
However, this process is disturbed in Alzheimer’s disease. In their study, Marc Aurel Busche, MD, PhD, from the Department of Psychiatry and Psychotherapy at TUM University Hospital Klinikum and TUM Institute of Neuroscience, and Arthur Konnerth, PhD, from the TUM Institute of Neuroscience, examined mice to observe how beta-amyloid plaques, which are also visible in humans, directly impair slow wave activity.
They found that on a molecular level, a precise balance between the excitation and inhibition of nerve cells must be maintained for the waves to spread correctly throughout the brain. In Alzheimer’s, the protein deposits disturb this balance, reducing nerve cell inhibition.
“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,” said Dr. Busche.
The researchers then treated the defect with medication. They gave tiny amounts of benzodiazephines, sleep-inducing drugs known to boost inhibitory influences in the brain, to the mice. With the medication, the sleep slow waves were able to spread out correctly. Subsequent experiments showed that the medication also improved the mice’s learning performance.
This is just a first step on the way to finding an effective treatment of Alzheimer’s disease, but these findings are noteworthy for two main reasons. First, mice and humans have the same sleep oscillations in the brain, meaning the results are transferable. Second, these waves can be recorded with a standard EEG monitor, meaning that impairment can be diagnosed early.
Busche MA, Konnerth A et al. Rescue of long-range circuit dysfunction in Alzheimer’s disease models. Nature Neuroscience. 2015; doi:10.1038/nn.4137.