Breathing CO2 May Help the Brain Clear Toxic Proteins in Parkinson’s Disease

A team of researchers, led by neuropsychologist Sephira Ryman, PhD, associate professor at the Mind Research Network (MRN), part of Touro University’s Lovelace Biomedical Research Institute and the University of New Mexico, Department of Neurology, is exploring how to boost this system, called the glymphatic pathway.

Her team studied how breathing carbon dioxide (CO₂) intermittently can boost the glymphatic pathway and help the body get rid of the proteins. Specifically, they investigated how CO₂ could be used to dilate and constrict the brain’s blood vessels, which in turn drives the movement of cerebrospinal fluid through brain tissue to clear unwanted proteins.

Their research was published in npj Parkinson’s Disease.

The glymphatic pathway is most active when people are deeply asleep. In this state, breathing slows down and the brain exhibits slow changes in blood flow, which drive the glymphatic pathway. However, for people with Parkinson’s, who often experience sleep disturbances, this waste removal process may be impaired, leading to a buildup of toxic proteins, like α-synuclein, and in some patients, amyloid beta and tau proteins—these are also implicated in Alzheimer’s disease.

In a prior study, Dr. Ryman found that a large number of people with Parkinson’s disease have a reduced and delayed response to intermittent CO₂ exposure.

“At the time, we were trying to understand how a reduced and delayed blood flow response may influence the pathophysiology of Parkinson’s disease,” said Ryman.  “Once we understood the role of glymphatic clearance in Parkinson’s disease, that is when we realized that we may be able to mimic, in the awake state, the glymphatic clearing response that typically occurs deep sleep using intermittent CO₂.” Senior author on a subsequent review paper, Dr. Henry Lin, was instrumental in integrating the human and animal research, revealing the critical insight the shaped the direction of the research.       

As proof of concept, the team administered alternating doses of room air with higher-than-normal concentrations of CO₂. They not only succeeded in reproducing the rhythmic response of the blood vessels of the brain, but blood samples following the intervention contained increased levels of brain proteins implicated in Parkinson’s and Alzheimer’s disease. This suggests that the potentially toxic proteins were flushed from the brain.

This novel strategy for enhancing the glymphatic system could potentially help preserve brain function, improve cognition, and reduce the risk of cognitive decline in people with Parkinson’s and potentially those with other neurodegenerative diseases like Alzheimer’s.

Ryman and her colleagues have called for more research to fine tune the protocol for CO₂ exposure.

They are investigating whether intentionally practicing controlled breathing practices, such as slow abdominal breathing, might be a way to enhance the glymphatic system and preserve brain function. Breathing practices may influence the glymphatic system through multiple physiological mechanisms, including regulation of carbon dioxide levels and changes in thoracic pressure that help facilitate the return of blood from the brain to the body. Ryman and her colleagues published another paper in the Journal of Cerebral Blood Flow and Metabolism detailing how controlled breathing and intermittent CO₂ can harness the glymphatic pathway.

“In addition to highlighting the potential for controlled breathing practices to facilitate waste clearance, these findings raise the intriguing possibility that rhythmic, controlled CO₂ exposures may serve as a direct and potentially more effective modulator of glymphatic function,” the authors wrote.