Enhancing Lymphatic Drainage Restores Memory in Aged Mice

As humans age, the brain’s ability to clear waste products declines, a process thought to contribute to the onset and progression of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Researchers at Washington University School of Medicine in St. Louis have found that enhancing the brain's waste-drainage system improves memory in aged mice.

Published March 21 in Cell, the findings suggest that stimulating meningeal lymphatic vessels – a network that clears brain waste via the lymphatic system – may present a new therapeutic approach for age-related cognitive decline, bypassing the difficulty of delivering drugs across the blood-brain barrier.

Restoring drainage improves memory performance

The study focused on the meningeal lymphatics, vessels located in the tissue surrounding the brain that direct fluid and waste toward the lymph nodes. Discovered nearly a decade ago, these vessels are involved in immune surveillance and waste clearance. As these pathways become less efficient with age – typically starting around age 50 – waste accumulates in the brain.

To test whether improving waste clearance could influence memory, the researchers treated aged mice with a compound that promotes growth and function of lymphatic vessels. They assessed the animals' memory using a simple object recognition test. Mice that had received the treatment spent more time exploring new objects than familiar ones, indicating improved memory function compared to untreated controls.

Linking immune signals to cognitive decline

Beyond the behavioral findings, the researchers explored the impact of impaired drainage on brain inflammation. When lymphatic drainage was disrupted, the burden shifted to microglia, the brain’s resident immune cells. These cells became overactive and began releasing interleukin-6 (IL-6), a signaling protein associated with inflammation. Elevated IL-6 levels were linked to disruptions in neuronal signaling patterns and contributed to impaired memory.

Following treatment, IL-6 levels decreased, and neuronal activity patterns normalized, restoring key brain communication functions that had been degraded in aging mice. These observations suggest that the physical removal of waste through enhanced lymphatic flow may reduce inflammatory stress on the brain.

Implications for therapy development

Unlike many neurological treatments that must cross the blood-brain barrier, the approach outlined in this study involves targeting lymphatic vessels located outside the brain. This could simplify treatment delivery and expand therapeutic options for neurodegenerative diseases or age-associated memory decline.

“The physical blood-brain barrier hinders the efficacy of therapies for neurological disorders. By targeting a network of vessels outside of the brain that is critical for brain health, we see cognitive improvements in mice, opening a window to develop more powerful therapies to prevent or delay cognitive decline.”

Dr. Johnathan Kipnis.

While the findings are currently limited to mice, they provide a mechanistic basis for pursuing lymphatic modulation as a strategy to support healthy brain aging in humans. Further research will be required to determine whether similar effects can be observed in people and whether long-term outcomes are beneficial.

Reference: Kim K, Abramishvili D, Du S, et al. Meningeal lymphatics-microglia axis regulates synaptic physiology. Cell. doi: 10.1016/j.cell.2025.02.022

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source. Our press release publishing policy can be accessed here.

This content includes text that has been generated with the assistance of AI. Technology Networks' AI policy can be found here.