The Refuse Removal System of the Sleeping Brain

by Kate Morris

Sleep. We all need it, yet few of us get enough of it. Now more than ever before the importance of sleep in protecting and prolonging the health of the brain is evident. With neurodegenerative diseases being among the most prevalent in the world today, maintaining cognitive function throughout an individual’s life in the hope of escaping neurological decline is a prominent focus of scientific research. The build-up of neurotoxic waste, such as the protein amyloid beta, in the brain is a major factor in the development of these disorders. Therefore, the recent discovery of a system that can clean the brain more efficiently during sleep, the glymphatic system, was pivotal. Reviewed by Hauglund, Pavan &
Nedergaard (2020), crucial factors influencing this system – which has been referred to as a garbage truck within the brain (Nedergaard, 2013) – are identified and compared, illustrating the biological necessity of sleep and optimal glymphatic clearance in warding off neurodegenerative disease.

Original research by Xie et al. (2013) observed the flow of CSF into the brain in live mice using powerful microscopy. Hablitz et al. and Winer et al. then studied the impact of brain waves during sleep and wakefulness on glymphatic flux and on amyloid beta levels in the brain, respectively. Finally, microscopic analysis was done by Mestre et al. (2018) on the movement of a fluorescent marker in the CSF of mice with and without distinct perivascular AQP4 channel expression. These channels are little filters that are crucial for allowing adequate flow of CSF into brain tissue.

Greater glymphatic ‘flushing’ of the brain was found to occur during sleep owing to brain wave activity and hormone levels characteristic of this state (Figure 1). Brain wave activity characteristic of wakefulness in turn foresaw higher levels of amyloid beta in the brain, correlating with poor sleep quality – which reciprocally affects amyloid beta levels. Additionally, mice lacking distinct perivascular AQP4 expression experienced a reduction in glymphatic clearance (Figure 2).

These results emphasize the importance of sleep and the quality thereof in
maintaining efficient glymphatic clearance of the ‘garbage’ in the brain,
and preserving cognitive function throughout one’s life. With 25 to 60% of
patients with neurodegenerative disorders such as Alzheimer’s Disease
experiencing dysfunctional sleep, future research on means to increase glymphatic clearance will be indispensable to the continuing fight against cognitive decline.


  1. Hauglund, N., Pavan, C. & Nedergaard, M. 2020. Cleaning the sleeping brain – the potential restorative function of the glymphatic system. Current Opinion in Physiology, 15: 1-6.
  2. Mestre, H. et al. 2018. Aquaporin-4-dependent glymphatic solute transport in the rodent brain. eLife, 7: e40070.
  3. Nedergaard, M. 2013. Garbage truck of the brain. Science, 340: 1529-1530.
  4. Xie, L. et al. 2013. Sleep drives metabolite clearance from the adult brain. Science, 342:373-377.

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