As aging bodies decline, the brain loses the ability to cleanse itself of waste, a scenario that scientists think could be contributing to neurodegenerative conditions such as Alzheimer’s disease and Parkinson’s disease, among others. Now, researchers at Washington University School of Medicine in St. Louis report they have found a way around that problem by targeting the network of vessels that drain waste from the brain. Rejuvenating those vessels, they have shown, improves memory in old mice.
The study, published online March 21 in the journal Cell, lays the groundwork to develop therapies for age-related cognitive decline that overcome the challenges faced by conventional medications that struggle to pass through the blood-brain barrier to reach the brain.
“The physical blood-brain barrier hinders the efficacy of therapies for neurological disorders,” said Jonathan Kipnis, PhD, the Alan A. and Edith L. Wolff Distinguished Professor of Pathology & Immunology and a BJC Investigator at WashU Medicine. “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.”
Waste removal improves memory
Kipnis is an expert in the blossoming field of neuroimmunology, the study of how the immune system affects the brain in health and disease. A decade ago, Kipnis’ lab discovered a network of vessels surrounding the brain — known as the meningeal lymphatics — in mice and humans that drains fluid and waste into the lymph nodes, where many immune system cells reside and monitor for signs of infection, disease or injury. He and colleagues also have shown that some investigational Alzheimer’s therapies are more effective in mice when paired with a treatment that improves drainage of fluid and debris from the brain.
Beginning at about age 50, people start to experience a decline in brain fluid flow as part of normal aging. For the new study, Kipnis collaborated with Marco Colonna, MD, the Robert Rock Belliveau, MD, Professor of Pathology, and asked if enhancing the function of an old drainage system can improve memory.