Glymphatic Clearance Of Brain Substances Driven By Vasomotion

Vasomotion, the spontaneous oscillation in tone of blood vessel walls, independent of heart beat, innervation or respiration, pushes the clearance of substances from the brain, investigators at Massachusetts General Hospital (MGH) have found.

The findings suggest that targeting and enhancing this process may promote prevention or treatment of amyloid-beta accumulation. In Alzheimer’s disease, amyloid-beta protein fragments agglomerate in the tissue and blood vessels of the brain, presumably because of defective clearance mechanisms.

“We were able to show for the first time that large dilations and contractions of vessels that happen spontaneously at an ultra-low frequency are a major driving force to clear waste products from the brain,”

lead author Susanne van Veluw, Ph.D., an investigator in the department of Neurology at MGH, explained.

Clearance Impaired

The researchers injected a fluorescently labeled carbohydrate called dextran into the brains of awake mice, then conducted two-photon microscopy imaging tests to follow its clearance. Their experiments showed that vasomotion was key for clearing dextran from the brain and stimulating an increase of the amplitude of these vessel pulsations could increase clearance.

Additionally, in mice with cerebral amyloid angiopathy, a condition that causes amyloid-beta to build up in the walls of the brain’s blood vessels, vessel pulsations were hindered and clearance rates were reduced.

“Our findings highlight the importance of the vasculature in the pathophysiology of Alzheimer’s disease. If we direct therapeutic strategies towards promoting healthy vasculature and therefore improve clearance of amyloid-beta from the brain, we may be able to prevent or delay the onset of Alzheimer’s disease in the future,”

Dr. van Veluw said.

[1] Susanne J. van Veluw, Steven S. Hou, Maria Calvo-Rodriguez, Michal Arbel-Ornath, Austin C. Snyder, Matthew P. Frosch, Steven M. Greenberg, Brian J. Bacskai. Vasomotion as a Driving Force for Paravascular Clearance in the Awake Mouse Brain. Neuron; DOI:https://doi.org/10.1016/j.neuron.2019.10.033