New Hope for Alzheimer’s: Fixing Brain Waste

Alzheimer's, Parkinson's, and other neurological disorders are sometimes referred to as "dirty brain" diseases because they involve the brain's difficulty in clearing away harmful waste. Aging is a major risk factor for these conditions, as the brain's ability to remove toxic substances diminishes over time. However, recent findings in mice suggest that it is possible to reverse these age-related changes and restore the brain's waste-clearing functions.

Douglas Kelley, Ph.D., a professor of Mechanical Engineering at the University of Rochester's Hajim School of Engineering and Applied Sciences, noted that the study shows that improving the function of cervical lymph vessels can significantly boost the brain’s ability to clear waste in older individuals. This improvement was achieved using an existing clinical drug, pointing to a potential new treatment strategy. Kelley, along with Maiken Nedergaard, MD, DMSc, co-director of the University’s Center for Translational Neuromedicine, co-authored the study published in Nature Aging.

The glymphatic system, identified by Nedergaard and her team in 2012, is the brain's unique method for waste removal. It uses cerebrospinal fluid (CSF) to flush out excess proteins generated by active neurons and other brain cells. This system is crucial for managing diseases associated with protein accumulation, like Alzheimer's (which involves beta amyloid and tau proteins) and Parkinson's (marked by alpha-synuclein).

In young, healthy brains, the glymphatic system efficiently clears these toxic proteins. However, as people age, this system becomes less effective, increasing the risk of these diseases.

The research involved tracking the journey of CSF through the lymphatic system to the kidneys for processing. Using advanced imaging and particle tracking techniques, the researchers mapped out the path of CSF through the cervical lymph vessels in the neck, revealing how half of the waste-laden CSF exits the brain.

They found that these lymph vessels have tiny pumps called lymphangions that help move the fluid. As mice age, the contractions of these lymphangions decrease and their valves start to fail, leading to a 63% reduction in the speed of waste removal from the brain compared to younger mice.

The team tested prostaglandin F2α, a drug commonly used to induce labor and known to enhance smooth muscle contraction. Applying this drug to the cervical lymph vessels in older mice restored the contraction rate and waste removal efficiency to levels similar to those in younger mice.

Kelley emphasized that these vessels, located near the skin’s surface, are vital for waste removal, and their function can now be enhanced. This approach, potentially combined with other treatments, could form the basis for new therapies for neurodegenerative diseases.