The Brain’s Waste Removal System

The brain consumes over a quarter of an ounce of protein and more than one fifth of the total energy used by the body each day. The protein is not completely consumed and wastes must somehow be eliminated from the brain. Until just a couple of years ago, scientists believed that some sort of degradation of wastes took place in brain cells. However, now based on the work or Steven Goldman and Maiken Nedergaar both of the University of Rochester building on the work of others we now know that the brain has its very own waste elimination system.

In most of the body a system of fluid-carrying vessels, the lymphatic system eliminates protein waste from tissues. Drs. Goldman and Nedergaar discovered that the perivascual space in the brain is a neural lymphatic system that provides a conduit for cerebrospinal fluid. The scientists called the intricate system of vessels that snakes throughout the brain the glymphatic system, the brains lymphatic system. The brains blood vessels are surrounded by perivascular spaces. These are sleeves that surround every blood vessel. The outer wall of these sleeves consist of extensions from a specialized cell called astrocyte. These astrocytes are support cells within the neural network. Now we know that the end feet of these cells complexly surrounds the arteries, veins, capillaries and spinal cord that clear and allows for the transport of fluid throughout the brain.

The scientists used a chemical dye to stain the cerebrospinal fluid and microscopic techniques enabled them to see deep inside a live brain. They found that pulsations in the brain arterial system from the heart pumping blood drives the cerebrospinal fluid through the perivascular space through the area between brain cells and finally to the perivascular space around the veins to clear the waste from the brain. Using astrocytes as conduits, the cerebrospinal fluid moved through the brain tissue where it picked up the discarded proteins such as beta-amyloid peptides which are associated with Alzheimer’s disease.

In Alzheimer’s disease aggregates of beta-amyloid form plaques between brain cells that is believed to contribute to the disease process. The scientists found that in a healthy brain beta-amyloid is cleared from the brain by the glymphatic system. These proteins and potentially others associated with neurodegenerative diseases could build up is the glymphatic system were to malfunction.

In a series of studies using mice that they trained to sit still under the microscope while awake the scientists were able to study and compare the flows of cerebrospinal fluid in the glymphatic system in awake and asleep mice. It seems the mice grew bored and fell asleep and the scientists were able to watch while tracer chemicals moved through the glymphatic system and compare awake and asleep in the same mice . It turns out that the cerebrospinal fluid falls dramatically in awake animals and rose by more than 60%-90% while the mice were asleep. The scientists were able to prove that sleep is essential to protein waste removal in the brain.

Much more research needs to be done, but the scientists working in this area are beginning to understand what triggers the increased removal of beta-amyloid peptides. We are still a very long way from effective treatments for Alzheimer’s, beta-amyloid plaque buildup, or synucleain protein buildup associated with other neurodegenerative diseases, but you can start by making sure you get plenty of sleep. Many Alzheimer’s patients experience sleep disturbances long before their dementia becomes apparent. The scientists have speculated that the sleep disturbances may not be a side effect of Alzheimer’s, but a contributing factor to the disease.