Breakthrough in restoring brain’s waste-clearing provides hope for Alzheimer’s

A new animal study has found a way to restore the brain’s waste-clearing process in mice, offering a potential treatment strategy for neurological disorders where the brain struggles to clear out harmful waste such as Alzheimer’s and Parkinson’s.

Ageing is a key risk factor for diseases such as Alzheimer’s and Parkinson’s because, as we age, our brain’s ability to remove toxic build up slows down. However, new research in mice demonstrates that it’s possible to reverse age-related effects and restore the brain’s waste-clearing process.

The glymphatic system is the brain’s unique waste removal process that uses cerebrospinal fluid (CSF) to wash away excess proteins generated by energy hungry neurons and other cells in the brain during normal activity.

This discovery, first described by Maiken Nedergaard, MD, DMSc, co-director the University’s Center for Translational Neuromedicine and her colleagues in 2012, pointed the way for potential new approaches to treat diseases commonly associated with the accumulation of protein waste in the brain, such Alzheimer’s (beta amyloid and tau) and Parkinson’s (alpha-synuclein).

In healthy and young brains, the glymphatic system does a good job of flushing away these toxic proteins, however, as we age, this system slows, setting the stage for these diseases.

Speaking on the new research, Douglas Kelley, PhD, a professor of Mechanical Engineering in the University of Rochester Hajim School of Engineering and Applied Sciences and lead author of the study, commented: “This research shows that restoring cervical lymph vessel function can substantially rescue the slower removal of waste from the brain associated with age.

“Moreover, this was accomplished with a drug already being used clinically, offering a potential treatment strategy.”

The study has been published in Nature Aging.

Drawing waste from the brain

Once laden with protein waste, CSF in the skull needs to make its way to the lymphatic system and ultimately the kidneys, where it is processed along with the body’s other waste.

The new research combines advanced imaging and particle tracking techniques to describe for the first time in detail the route via the cervical lymph vessels in the neck through which half of dirty CSF exits the brain.

In addition to measuring the flow of CSF, the researchers were able observe and record the pulsing of lymph vessels in the neck that helps draw CSF out of the brain.

“Unlike the cardiovascular system which has one big pump, the heart, fluid in the lymphatic system is instead transported by a network of tiny pumps,” said Kelley.

The researchers found that as the mice aged, the frequency of contractions decreased, and the valves failed. As a result, the speed of dirty CSF flowing out of the brains of older mice was 63% slower compared to younger animals.

The team then set out to see if they could revive the lymphangions and identified a drug called prostaglandin F2α, a hormone-like compound commonly used medically to induce labour and known to aid smooth muscle contraction.

The lymphangions are lined with smooth muscle cells, and when the researchers applied the drug to the cervical lymph vessels in older mice, the frequency of contractions and the flow of dirty CSF from the brain both increased, returning to a level of efficiency found in younger mice.

“These vessels are conveniently located near the surface of the skin, we know they are important, and we now know how to accelerate function,” said Kelley.

“One can see how this approach, perhaps combined with other interventions, could be the basis for future therapies for these diseases.”