What is the Glymphatic System?

by Brooklin White MS, RDN, LDNNews
Brain on a purple background

The human body is a miraculous orchestra composed of chemical reactions that constantly work to keep us alive and well. The cardiovascular system, for instance, transports nutrients and oxygen-rich blood to all parts of the body and the digestive system breaks down and absorbs nutrients from food and liquids. One of the lesser known systems is the lymphatic system, known as a part of the immune system and functions to maintain bodily fluid levels, fight infection, and remove waste. Most tissues of the body use the lymphatic system for removing cellular protein debris and toxic molecules from peripheral organs which are then transported to the bloodstream and brought to the liver and kidneys to be eliminated from the body (1). 

The only organ the lymphatic system is unable to reach however is the brain. The brain, similar to other organs, has high metabolic demands and is constantly building and breaking down its own proteins. If the lymphatic system lacks access to the brain, then you might be thinking, how does the brain recycle its cellular proteins and remove its toxic components? It was only recently discovered that cerebrospinal fluid (CSF), a fluid made in the ventricles of the brain and primarily known to act as a cushion for the brain, would also act as as the brains very own lymphatic system, which is known today as the glymphatic system. In the glymphatic system, CSF encircles brain blood vessels and accesses the rest of the brain through cells called glia, which grant CSF entry to neurons and other brain cells to collect protein debris. This debris is then removed from the surrounding brain cells and taken through the very same ducts used by the lymphatic system for disposal (2).   

The Relationship Between the Glymphatic System, Alzheimer’s Disease and Lifestyle Factors

It is important to consider that protein accumulation in the brain is a general feature of neurodegenerative disorders. One of the main hypotheses of Alzheimer's pathology, for example, is the accumulation of β-amyloid proteins, which can aggregate together and eventually kill the neurons responsible for memory formation, ultimately leading to dementia. The recent discovery of the glymphatic pathway is crucial for Alzheimer’s research since it has the capability of clearing excess β-amyloid proteins (3), especially while we sleep.

Sleep is essential for life and restorative in many ways. It is essential for immunity, cellular regeneration and even memory formation (4, 5). Research has shown that sleep dramatically enhances glymphatic activity (6). Sleep has been associated with a 60% increase in interstitial space within the brain, resulting in increased clearance of β-amyloid (7) while poor sleep has been associated with the buildup of β-amyloid and tau proteins in addition to brain cell damage and inflammation (8). A study by Zhang et. al. found that sleep deprivation in mice led to dendrite loss (dendrites are the part of neurons where synaptic function takes place and are thus essential for memory formation)(9, 10). The data therefore indicate that those with poor sleep quality are at a higher risk of developing Alzheimer’s disease. 

In one of our recent blog posts, we discuss how exercise is one of the best ways to increase blood flow and oxygenation in the brain which can lead to higher levels of cognitive function (11, 12). Research has now shown that exercise positively affects the function of the glymphatic system. A 2017 study showed that exercised mice had heightened glymphatic activity when compared to the sedentary mice by increasing the influx of CSF (13).

What’s the Takeaway?

As with many organ and organ system functions, aging diminishes glymphatic function (6). This is potentially due to decreased CSF, decreased flexibility/pulsing of brain arteries and normal atrophy of brain cells (14). Certain MRI studies have also shown that damage to the brain following a traumatic brain injury severely impairs glymphatic function (15). This research indicates that the accumulation of β-Amyloid might be caused by the impairment of the glymphatic system. 

This data emphasizes the importance of organ reserve, the concept that our organs are exceptional at clearing out toxins and maintaining health when we are young, but slowly start to lose their stamina as we age (16). The more we can incorporate healthy lifestyle habits that support brain health (sleep, exercise and nutrition, for example) the more we can support the healthspan and longevity of brain functions and ultimately our glyphosate system. To learn more about how you can best maintain organ reserve and incorporate an individualized nutrition and lifestyle plan to reverse or prevent Alzheimer’s disease, please reach out to the Amos Institute today. 

References 

  1. Moore, J. E., Jr, & Bertram, C. D. (2018). Lymphatic System Flows. Annual review of fluid mechanics, 50, 459–482. https://doi.org/10.1146/annurev-fluid-122316-045259
  2. Sweeney, M. D., & Zlokovic, B. V. (2018). A lymphatic waste-disposal system implicated in Alzheimer's disease. Nature, 560(7717), 172–174. https://doi.org/10.1038/d41586-018-05763-0
  3. Iliff, J. J., Wang, M., Liao, Y., Plogg, B. A., Peng, W., Gundersen, G. A., Benveniste, H., Vates, G. E., Deane, R., Goldman, S. A., Nagelhus, E. A., & Nedergaard, M. (2012). A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Science translational medicine, 4(147), 147ra111. https://doi.org/10.1126/scitranslmed.3003748
  4. Buzsáki G. (1998). Memory consolidation during sleep: a neurophysiological perspective. Journal of sleep research, 7 Suppl 1, 17–23. https://doi.org/10.1046/j.1365-2869.7.s1.3.
  5. Huber, R., Ghilardi, M. F., Massimini, M., & Tononi, G. (2004). Local sleep and learning. Nature, 430(6995), 78–81. https://doi.org/10.1038/nature02663
  6. Jessen, N. A., Munk, A. S., Lundgaard, I., & Nedergaard, M. (2015). The Glymphatic System: A Beginner's Guide. Neurochemical research, 40(12), 2583–2599. https://doi.org/10.1007/s11064-015-1581-6
  7. Xie, L., Kang, H., Xu, Q., Chen, M. J., Liao, Y., Thiyagarajan, M., O'Donnell, J., Christensen, D. J., Nicholson, C., Iliff, J. J., Takano, T., Deane, R., & Nedergaard, M. (2013). Sleep drives metabolite clearance from the adult brain. Science (New York, N.Y.), 342(6156), 373–377. https://doi.org/10.1126/science.1241224
  8. Sprecher, K. E., Koscik, R. L., Carlsson, C. M., Zetterberg, H., Blennow, K., Okonkwo, O. C., Sager, M. A., Asthana, S., Johnson, S. C., Benca, R. M., & Bendlin, B. B. (2017). Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively normal adults. Neurology, 89(5), 445–453. https://doi.org/10.1212/WNL.0000000000004171
  9. Zhang, J., Zhu, Y., Zhan, G., Fenik, P., Panossian, L., Wang, M. M., Reid, S., Lai, D., Davis, J. G., Baur, J. A., & Veasey, S. (2014). Extended wakefulness: compromised metabolics in and degeneration of locus ceruleus neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience, 34(12), 4418–4431. https://doi.org/10.1523/JNEUROSCI.5025-12.2014
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  12. Dustman, R. E., Ruhling, R. O., Russell, E. M., Shearer, D. E., Bonekat, H. W., Shigeoka, J. W., Wood, J. S., & Bradford, D. C. (1984). Aerobic exercise training and improved neuropsychological function of older individuals. Neurobiology of aging, 5(1), 35–42. https://doi.org/10.1016/0197-4580(84)90083-6
  13. von Holstein-Rathlou, S., Petersen, N. C., & Nedergaard, M. (2018). Voluntary running enhances glymphatic influx in awake behaving, young mice. Neuroscience letters, 662, 253–258. https://doi.org/10.1016/j.neulet.2017.10.035
  14. Society of Neuroscience. (2021). Understanding the Glymphatic system. Retrieved September 7, 2021, from https://neuronline.sfn.org/scientific-research/understanding-the-glymphatic-system
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