Study Shows New Links Between Brain’s Waste Drainage System and Neurodegenerative Disorder

Feb. 7, 2024
The study also found that our brain may become more susceptible to “leaks” in its waste drainage system as we age

A recent study of the brain’s waste drainage system has revealed that waste fluid may be able to leave the brain more easily than previously thought.

The study, performed by researchers from Washington University in St. Louis, collaborating with investigators at the National Institute of Neurological Disorders and Stroke (NINDS), which is part of the National Institute of Health (NIH), “discovered a direct connection between the brain and its tough protective covering, the dura mater. These links may allow waste fluid to leave the brain while also exposing the brain to immune cells and other signals coming from the dura.” Conventional wisdom has long been that “the brain is cut off from its surroundings by a series of protective barriers, keeping it safe from dangerous chemicals and toxins lurking in the environment” – this new research challenges that notion.

A group led by NINDS’s Daniel S. Reich, M.D., Ph.D., used “high-resolution magnetic resonance imaging (MRI) to observe the connection between the brain and body’s lymphatic systems in humans.” Meanwhile, a group led by Jonathan Kipnis, Ph.D., independently used “live-cell and other microscopic brain imaging techniques to study these systems in mice.”

The researchers “scanned the brains of a group of healthy volunteers” who received an injection of gadobutrol, which is a magnetic dye used to “visualize disruptions in the blood brain barrier.” A ring of dye “appeared around large veins [that are known to carry blood away from the brain] that slowly spread out over time, suggesting that fluid could make its way through the space around those large veins where they pass through the arachnoid barrier on their way into the dura.” Meanwhile, Kipnis’s lab made similar observations in mice.

The two labs found a “’cuff’ of cells that surround blood vessels as they pass through the arachnoid space.” These areas “appear to act as areas where fluid, molecules, and even some cells can pass from the brain into the dura and vice versa.” In certain disorders like Alzheimer’s disease, clogs at these areas, called arachnoid cuff exit (ACE) points, can cause “disease-causing proteins to build up.” Kipnis emphasized that “if we can find a way to clean these clogs, it’s possible we can protect the brain.”

Kipnis also found that these ACE points could break down over time if exposed to disorders “where the immune system attacks the myelin in [the] brain,” pointing the way forward for further research to determine how to “tightly regulate” these points.

Reich found that, in older participants, “more dye leaked into the surrounding fluid and space around the blood vessels,” demonstrating a link between age and the “leakiness of ACE points.” These observations fit what has already been observed in aging mice and in autoimmune disorders like multiple sclerosis. This discovery could also “help explain why our risk for developing neurodegenerative diseases increases as we get older.”

NIH’s website has the news release.