Stony Brook University Hospital researchers have found that the brain’s glymphatic pathway, a process that clears waste and solutes from the brain, can contribute to the development of Alzheimer’s disease and can also provide a possible strategy to evaluate the disease.

“The glymphatic pathway functions as a waste clearance pathway in the brain,” Dr. Jeffrey Iliff, an assistant professor in the department of anesthesiology and perioperative medicine at Oregon Health & Science University, said.

Dr. Helene Benveniste, a clinical anesthesiologist at Stony Brook Hospital, says the new technique provides a three-dimensional view of the glymphatic pathway. (ROLYNE JOSEPH / THE STATESMAN)
Dr. Helene Benveniste, a clinical anesthesiologist at Stony Brook Hospital, says the new technique provides a three-dimensional view of the glymphatic pathway. (ROLYNE JOSEPH / THE STATESMAN)

Iliff and Dr. Maiken Nedergaard, from the University of Rochester Medical Center School of Medicine and Dentistry, coined the term glymphatic pathway. They examined the cerebrospinal fluid (CSF) filters through the brain and exchanges with interstitial fluid (ISF), a solution that cleans and surrounds the cells of multicellular animals.

Iliff suggested that the glymphatic pathway removes extracellular proteins, fluids and metabolic waste from the brain. “The brain has neurons and it fires electrical signals,” Iliff said. “The brain takes care of the glial cell.”

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Iliff explained that the glial cell supports and protects neurons in the brain and other parts of the nervous system. The glial cell provides nutrients and oxygen to neurons and also eliminates dead neurons and destroys pathogens.

The glymphatic pathway has the CSF that allows entrance to the brain’s parenchyma, a functional tissue in any body organ, with a clearance device for the removal of ISF and extracellular solutes from the brain and spinal cord, according to the Journal of Clinical Investigation’s website.

The ISF and the astrocytic aquaporin-4 (AQP4), a protein that conducts water to cell membrane, helps the clearance of soluble proteins, waste products and excess extracellular fluid. Researchers were able to discover how the glymphatic pathway had an effect on the brain.

“Since Alzheimer’s disease is characterized by amyloid plaques and tau, it is logical to then assume that if one can find a way to maintain glymphatic pathway efficiency, plaques and tau would not build up and therefore one would not be afflicted with Alzheimer’s disease,” Dr. Helene Benveniste, a clinical anesthesiologist at Stony Brook University Hospital, said.

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Researchers were able to examine the brain’s imaging through enhanced magnetic resonance imaging (MRI), a technique that shows internal structures of the body in details.

Researchers used an MRI to evaluate the functionality of the glymphatic pathway. The MRI allowed examiners to evaluate  susceptible certain subjects and the effects of exchanges  of solutes and waste from the brain.

The brain’s glymphatic pathway can contribute to the development of the disease. Researchers do not yet know how the brain’s glymphatic pathway can contribute to the development of the disease.

The cerebral spinal fluids through the brain and exchanges with interstitial fluid are similar to lymphatic vessels, tubular structures that carry lymph and white blood cells. The interstitial fluids are similar to lymphatic vessels and clear waste from other organs of the body.

“CSF exchanges with brain interstitial fluid and likely solutes and waste is dumped in the large veins of the brain and/or lymphatic nodes outside the brain,” Benveniste said.

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But examiners could not visualize the brain wide flow of the pathway with previous imaging techniques. Brain flow has been visualized before, but researchers have not been able to visualize glymphatic flow in the brain.

The glymphatic flow has a slow process and required a closed skull and in the current modality a contrast agent that is delivered into the CSF, Benveniste said.

Benveniste suggested that clinically relevant imaging technique can measure the glymphatic pathway. The technique provides a three-dimensional view of the glymphatic pathway that captures the movement of waste and solutes.

The imaging technique can help investigators determine the role of the pathway in clearing matter such as amyloid beta, amino acids that are the main deposits found in the brains of patients with Alzheimer’s disease and tau proteins, substances that are found in neurons to keep nerves from working properly, can affect brain processes.

Repetitive traumatic brain injuries can lead to a decrease in waste removal system.

“With repetitive traumatic brain injuries; astrocytes which comprise an important functional component of the glymphatic pathway becomes ‘reactive’ and they no longer function normally,” Benveniste said. “Thus the waste removal system also slows down.”

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Researchers conducted experiments with genetically modified mice and found that the glymphatic clearance system was able to remove soluble amyloid-beta from the brain interstitial fluid.

Benveniste insisted that the pathology of certain neurological conditions is associated with the accumulation of proteins and other extracellular accumulations. An example is the accumulation of amyloid plaques, sticky build up which accumulates outside of nerve cells, and tau in the interstitial space of gray.

Studies have shown that amyploid proteins consisting of proteins that are deposited on animal organs and tissues under abnormal conditions can be toxic to neurons.

Amyploid proteins and plaque deposits of proteins are among the characteristics of Alzheimer’s disease and are implicated in its development.

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