Brain Beta-Amyloid Levels Increase after Sleep Deprivation

What's the science?

Beta-amyloid is a protein that accumulates in the brain in Alzheimer’s disease and with aging. Sleep is thought to be important for clearance of beta-amyloid as a “waste product” and a lack of sleep over time has been associated with higher beta-amyloid in the brain. There is evidence that beta-amyloid is elevated in brain fluid in mice after acute sleep deprivation, however, it is not clear how acute sleep deprivation affects beta-amyloid levels in the human brain. This week in PNAS, Shokri-Kojori and colleagues use Positron Emission Tomography (PET) to assess whether beta-amyloid is elevated after short-term sleep deprivation in humans.

How did they do it?

PET imaging with a radiotracer called 18F-florbetaben which binds to beta-amyloid in the living human brain, was used to measure beta-amyloid levels in 20 healthy participants. Participants were scanned once after a healthy night of sleep and once after a night of sleep deprivation (no sleep) to compare beta-amyloid levels with and without proper sleep. Participants were given questionnaires related to their mood. Data about sleep history and quality were also collected. The authors hypothesized that beta-amyloid levels would be higher in the hippocampus (one of the first brain regions affected by Alzheimer’s disease) after one night of sleep deprivation and that a poor sleep history would be associated with higher beta-amyloid in brain regions known to be affected by Alzheimer’s disease: the medial prefrontal cortex, the hippocampus and the precuneus.

What did they find?

Beta-amyloid accumulation (measured with 18F-florbetaben) was higher in the right hippocampus after one night of sleep deprivation compared to after a good night’s sleep. The extent to which beta-amyloid increased varied between individuals. Mood was found to be worse after sleep deprivation, and this was correlated with the level of beta-amyloid in the regions showing elevated beta-amyloid such as the hippocampus. Reported hours of sleep per night was negatively correlated with beta-amyloid accumulation (i.e. higher sleep, lower beta-amyloid) in the right hippocampus and thalamus where acute sleep deprivation effects were seen. In a separate whole-brain regression analysis, hours of sleep was also negatively correlated with beta-amyloid levels in the putamen, parahippocampal gyrus and right precuneus (brain regions affected by beta-amyloid in Alzheimer’s disease) confirming that these are key regions affected by hours of sleep.

Brain, Servier Medical Art, image by BrainPost, CC BY-SA 3.0

What's the impact?

This is the first study to show that one night of sleep deprivation is associated with higher beta-amyloid in the human brain. This study also highlights the relationship between hours of sleep (self-reported sleep history) and beta-amyloid accumulation. This study emphasizes that sleep is important for regulating beta-amyloid levels and that sleep deprivation could be one risk factor for brain protein accumulation in Alzheimer’s disease and aging.

E. Shokri-Kojori et al., β-Amyloid accumulation in the human brain after one night of sleep deprivation. PNAS (2018).  Access the original scientific publication here.

Ripples During Slow-Wave Sleep Re-balance Neurons

What's the science?

Synapses in the brain are strengthened while awake and synaptic depression (weakening of the synapses) occurs during slow-wave sleep to rebalance synapses. This synaptic depression may help to selectively preserve memories, however, how it occurs during sleep is unclear. During slow-wave sleep, the hippocampus emits high frequency oscillations called “sharp-wave ripples” which reactivate the neurons involved in recent memories. Ripples could be required for synaptic depression during sleep, making “room” for new memories to form. This week in Science, Norimoto and colleagues test whether ripples are required for synaptic depression and subsequent memory formation in mice.

How did they do it?

They silenced sharp-wave ripple events during slow-wave sleep using optogenetic-feedback (i.e. every time a ripple event was detected, they inhibited the hippocampal neurons to reduce firing) in a group of test mice. They then recorded excitatory postsynaptic potentials (activity in the postsynaptic neurons) during slow-wave sleep and compared the test mice to control mice to determine whether synaptic depression during sleep was affected in the test mice. Mice then underwent a spatial object-recognition task. First, they explored an area containing two new objects, and then returned to the same location 2 hours later where one of the objects had moved. The authors compared the memory performance between test and control mice to determine whether disrupting the ripples had an effect on new memory acquisition.

What did they find?

The authors were able to successfully reduce almost all of the ripple events in the test mice. Control mice experienced depressed postsynaptic activity representing the expected synaptic depression that occurs during slow-wave sleep, while mice with the impaired ripple events did not show synaptic depression. Control mice showed normal memory performance, while mice with impaired ripple events were unable to identify a moved object in the spatial object recognition task, suggesting that they could not form new memories. The authors were also able to replicate the lack of synaptic depression by testing the effects of disrupting ripples in hippocampal tissue slices. They used in vitro and in vivo experiments to show that synaptic depression occurring during slow-wave sleep is mediated by NMDA receptors.

What's the impact?

This is the first study to link sharp-wave ripples during slow-wave sleep with synaptic depression and memory performance. Before this study, we did not understand the mechanism through which synaptic depression occurred during slow-wave sleep. We now know that ripples during slow-wave sleep are critical for balancing of synapses and for new memory formation.

H. Norimoto et al., Hippocampal ripples down-regulate synapses. Science (2018). Access the original scientific publication here.