Glymphatic System

What is it?

The glymphatic system, discovered in 2012 by Dr. Maiken Nedergaard, is the part of the lymphatic system that concerns the brain, that is responsible, among other things, for transporting cellular waste. In particular the glymphatic system transports waste such as beta-amyloid proteins and tau proteins which can create some harmful accumulations in dementia pathologies such as Alzheimer.
This system is cerebrospinal fluid also known as liquor, a liquid that surrounds the brain, feels in its empty parts and can also flow through a branched system made of canals (this was demonstrated by Nedergaard at the University of Rochester, United States).
The liquor flows through a perivascular space that surrounds the blood vessels, then it actually enters in the cerebral tissue to then finally reenter the perivascular canals. This process is possible thanks to the astrocyte pedicels in which there are pores permeable to water made of proteins called aquaporins. A year later Nedergaard made another very important discovery: this system is active especially during sleep.

How does it work?

Another important discovery Nedergaan made is the neuron's ability to shrink while sleeping which would increase the extracellular space, making it way easier for the liquor to penetrate the cerebral tissue.
What regulates this whole process?
Many mechanisms are responsible for this whole process, one of them being the neuron’s activity during sleep, in fact while sleeping many turn on in a synchronized way generating low frequency brain waves (between 0.5 and 8 Hertz). This is quite important, as a study conducted by Laura Lewis in 2019 at the University of Boston demonstrated, because more or less every 20 seconds a flow of either blood or liquor reaches the brain while it’s asleep and this rhythm matches the one of the low frequency brain waves that can be at times stronger or weaker. This happens because if a lot of neurons turn on together the energy needs increase consequently so does the quantity of blood that flows in the brain; on the other hand while the blood flow decreases in his place the liquor enters.
Another important factor that was discovered this time by Nedergaard team in 2025, is that while asleep, especially during deep sleep, the brainstem rhythmically releases norepinephrine, a neurotransmitter that shrinks blood vessels, making them move accordingly and forcing the cerebrospinal fluid to leak from the canals around the blood vessels into che brain tissue.
Then what does move the liquor when it reaches the brain tissue?
Well, according to Jonathan Kipnis' study at Washington University, in Missouri, it seems that those responsible for this phenomenon are charged particle's waves in extracellular space.

What does all of this have to do with dementia?

As I’ve said in the beginning of the essay in Alzheimer’s dementia beta-amyloid proteins accumulate in the brain. While an actual cure is quite far from being founded there are many ongoing studies such as the Bakker’s one that concentrates on the blood vessels and in particular the arteries's hypertension in the elderly that makes it harder for the vessels to contract and consequently push less liquor into the brain tissue. This hypertension could be caused by the presence of a proteic fragment called Medin, and if so is true the removal of it could help fight dementia.
Jonathan Kipnis on the other hand believes that the problem could be resolved by reinforcing the brain waves while sleeping through auditory stimuli or brain stimulation improving the liquor’s flow.
Maybe the most thrilling news comes from China where some surgeons such as Xie et al and Xia Li with her team performed surgery on patients affected by Alzheimer to connect the lymphatic vessels to the blood ones. The results have been truly amazing, as stated in the article written by Xia Li and the rest of the team, the procedure was done on six patients and they all showed in the span of 5 weeks great improvements in cognitive functions.

Anyway all these procedures are experimental and while they are fantastic steps forwards that bring us closer to a possible cure for this disease the only concrete thing we all can do more is sleep, I say at 1:00 a.m as I finish an essay.