Alzheimer’s, Parkinson’s, and various other neurological conditions are often referred to as “dirty brain” diseases. These diseases are characterised by the brain’s diminishing capacity to eliminate harmful waste. This issue becomes more pronounced with age as the brain’s efficiency in removing toxic build-up decreases. However, recent studies in mice have shown promising results in reversing these age-related impairments and reinstating the brain’s waste-clearing capabilities.
Douglas Kelley, PhD, a professor of Mechanical Engineering at the University of Rochester Hajim School of Engineering and Applied Sciences, shared insights into this groundbreaking research. “Our findings indicate that by restoring the function of cervical lymph vessels, we can significantly improve the brain’s ability to expel waste accumulating with age,” Kelley explained. The research, which Dr Kelley co-authored and was published in the journal ‘Nature Aging’, also involved Maiken Nedergaard, MD, DMSc, co-director of the University’s Center for Translational Neuromedicine.
The study builds on the discovery of the glymphatic system, first identified by Nedergaard and her team in 2012. This unique waste removal system in the brain leverages cerebrospinal fluid (CSF) to flush out surplus proteins that cells in the brain produce during regular activity. These findings have opened new avenues for potentially treating diseases like Alzheimer’s and Parkinson’s, which are linked to the accumulation of specific protein wastes in the brain. In younger and healthier brains, the glymphatic system effectively eliminates these toxic proteins; however, its efficiency wanes with age, predisposing individuals to these neurological diseases.
The recent study also provided a detailed description of the pathway through the cervical lymph vessels in the neck, which facilitates the expulsion of half of the CSF-containing protein waste from the brain. The researchers employed advanced imaging and particle tracking techniques to map this route and observed the rhythmic pulsing of lymph vessels that aid in drawing CSF out of the brain. Unlike the cardiovascular system, which relies on the heart as a central pump, the lymphatic system uses a network of small lymphangions. These are equipped with valves to prevent backflow and are connected sequentially to form lymph vessels.
The study revealed that as mice age, the contraction frequency of these lymphangitis diminishes, and their valves are prone to failure. This considerably slows the rate at which waste-laden CSF is expelled from the brain—by as much as 63 per cent in older mice compared to their younger counterparts.
To tackle this slowdown, the researchers experimented with prostaglandin F2α, a hormone-like compound routinely used in medical settings to induce labour and known for enhancing smooth muscle contractions. When applied to the cervical lymph vessels in older mice, this drug significantly increased the frequency of lymphangion contractions and the flow rate of CSF, restoring it to levels observed in younger mice.
Kelley expressed optimism about the implications of these findings, “Given the accessibility of these vessels just beneath the skin and their proven significance, this research not only deepens our understanding but also showcases a viable method to boost their function.” He speculated that this strategy, possibly in combination with other interventions, could lay the groundwork for future treatments aimed at combatting these “dirty brain” diseases.
More information: Ting Du et al, Restoration of cervical lymphatic vessel function in aging rescues cerebrospinal fluid drainage, Nature Aging. DOI: 10.1038/s43587-024-00691-3
Journal information: Nature Aging Provided by University of Rochester Medical Center
