Waste Management in the Brain May Shed Light on Dementia

Summary: When cerebral amyloid angiopathy is present, the brain diverts most of the waste-removing fluid away from the glymphatic system.

Source: Yale

A new study suggests that a contributing factor in dementia may come down to a double dose of bad waste management in the brain.

A research team led by Yale, Stony Brook University, and the University of Rhode Island found that the body’s systems for flushing waste out of the brain failed to work properly when faced with cerebral amyloid angiopathy (CAA), a condition in which the protein amyloid beta builds up in blood vessels in the brain. CAA is a leading cause of brain hemorrhage and is closely associated with Alzheimer’s disease. There is currently no effective treatment for the condition.

Dr. Helene Benveniste, a professor of anesthesiology at Yale School of Medicine and co-senior author of a new study in Nature Aging, says a main culprit in CAA may be an abnormal re-routing of cerebrospinal fluid (CSF) away from the brain’s glymphatic system. CSF normally flushes through the glymphatic system as a handy trash removal service.

Benveniste and her colleagues—including teams led by Allen Tannenbaum at Stony Brook and William Van Nostrand at the University of Rhode Island’s George & Ann Ryan Institute for Neuroscience—developed innovative MRI imaging techniques and computational methods of fluid dynamics to track the glymphatic system in rodents with CAA.

The researchers discovered that when the CAA disease is present, the brain appears to divert most of the waste-removing fluid away from glymphatic cleaning channels.

Credit: Yale

“When CSF does not go into the glymphatic channels, the brain does not get ‘cleaned,'” Benveniste said. “There is a lot of garbage that will rapidly build up, because fluid is not getting into the right channels to remove waste.”

The cause of this re-routing of the glymphatic system remains a mystery, the researchers said. One possibility might be that inflammation also sets in with CAA and cuts off normal glymphatic pathways in the brain.

This shows a diagram from the study
CSF flow speed becomes hyperdynamic with severe CAA. Credit: The researchers

But the glymphatic system is not the only waste disposal service in the brain being affected by CAA. The researchers discovered that the lymphatic system—a network of lymph vessels in the membranes covering the brain that drains to the lymph nodes in the neck—may likewise be impaired.

Although lymphatic drainage still occurs with CAA, the researchers found that the drainage is slowed down.

“Both systems, glymphatic and lymphatic, are being affected,” Benveniste said. “It’s not either-or. These systems are in communication with each other and both have to be maintained in order to have a healthy brain.”

The researchers said their findings may offer insight into possible treatment options for CAA that would restore normal fluid passage through the brain’s waste disposal system before the disease has taken hold.

About this dementia research news

Author: Jim Shelton
Source: Yale
Contact: Jim Shelton – Yale
Image: The image is credited to the researchers

Original Research: Closed access.
Cerebral amyloid angiopathy is associated with glymphatic transport reduction and time-delayed solute drainage along the neck arteries” by Xinan Chen et al. Nature Aging


Cerebral amyloid angiopathy is associated with glymphatic transport reduction and time-delayed solute drainage along the neck arteries

Cerebral amyloid angiopathy (CAA) is a common disease in older adults that contributes to dementia. In CAA, amyloid beta (Aβ) is deposited along either capillaries (type 1) or vessel walls (type 2), with the underlying pathophysiology incompletely understood.

Here, we developed imaging and analysis tools based on regularized optimal mass transport (rOMT) theory to characterize cerebrospinal fluid (CSF) flow dynamics and glymphatic transport in a transgenic CAA type 1 rat model.

We discovered that, in CAA, CSF moves more rapidly along the periarterial spaces that serve as influx routes to the glymphatic system. The observation of high-speed CSF flow currents in CAA was unexpected given the build-up of microvascular Aβ.

However, velocity flux vector analysis revealed that CSF currents in CAA are partly diverted away from the brain, resulting in overall decreased glymphatic transport. Imaging at the neck showed that drainage to the deep cervical lymph nodes occurs along the carotid arteries and is time delayed in CAA, implying that upstream connections to the meningeal lymphatics were altered.

Based on our findings we propose that, in CAA, both glymphatic transport and lymphatic drainage are compromised and that both systems represent therapeutic targets for treatment of CAA-related cognitive decline and dementia.

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