The Glymphatic System: Significance of Sleep in Clearing Protein Waste within the Mind

The glyphatic system, which is most active during sleep, clears the brain of protein waste, and the breakdown of this system over time can be linked to an increased risk of dementia, according to a review published in Science.

The glymphatic system, a highly organized cerebrospinal fluid transport system, exports excess interstitial fluid and proteins out of the brain via the glyphatic pathway. This pathway is an independent system of fluid transport based on perivascular spaces that are formed by the terminal feet of the astrocytes.

Aging typically leads to some form of protein aggregation in the brain that is linked to an increased risk of dementia. In addition, the quality of sleep decreases with age, which ultimately leads to a decrease in brain waste elimination. The study’s researchers suggested that sleep disorders in the elderly could significantly reduce the clearance of the export of cerebrospinal fluid and protein waste, and possibly accelerate the progression of neurodegeneration.

In animal models, glyphatic fluid transport and amyloid-β export are facilitated by the polarized expression of AQP4 in the vascular terminal feet of astrocytes. In humans, the genetic variation of AQP4 affects sleep and amyloid-β load. In other studies, a more common single nucleotide polymorphism of AQP4 has been linked to changes in slow-wave activity during non-REM sleep, which resulted in daytime sleepiness and changes in reaction times with prolonged wakefulness.

According to the review authors, the available research on the glyphatic system underscores the importance of a good night’s sleep in potentially assisting in the proper elimination of protein waste from the brain. They added that “the development of small molecule agonists with glymphatic discharge may offer ways to slow the progression of the disease in aggregation disorders,” but ultimately more research is needed.


Nedergaard M, Goldman SA. Glymphatic failure as the last common path to dementia. Science. 2020; 370 (6512): 50-50; 56. doi: 10.1126 / science.abb8739


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