2023 Alzheimer's Association Research Fellowship (AARF)
Crosstalk of Meningeal Lymphatics and the blood-brain barrier
How do the entry and exit systems to the brain work together to maintain a healthy brain environment in aging?
Steffen Storck, Ph.D.
Washington University in St.Louis
St. Louis, MO - United States
Background
The lymphatic system, which includes lymph nodes and lymphatic vessels, is a drainage system that the body uses to “flush out” unwanted substances. In the brain, these unwanted substances are removed through the blood-brain barrier (BBB), which tightly regulates what is allowed to go into and out of the brain. Studies have found that when the BBB is damaged, it becomes harder for waste to drain out of the brain’s lymphatic system, specifically the meningeal lymphatic vessels (MLVs). Recent studies suggest damage to the MLVs may lead to brain changes seen in Alzheimer’s.
To further study how the alteration of these “exit” and “entry” systems affect each other, researchers have developed advanced surgical and genetic techniques to test how damage to MLVs and the BBB impact brain health and cognition. Dr. Storck’s team found that when MLVs were damaged, the BBB becomes more "leaky," allowing things to cross into the brain more easily. They also found that an increase in interleukin-1 beta (Il1𝛽) cytokines (special proteins that influence how our immune system functions) were responsible for this effect. When the researchers looked at brain tissue from individuals who had Alzheimer’s, they also saw in increase in Il1𝛽. Now, they want to understand which cells in the body are responsible for this increase in Il1𝛽 as well as assess how damage to MLVs or enhanced functioning of MLVs affects Alzheimer’s like brain changes and functioning of the BBB.
Research Plan
Dr. Storck and team will expand on their previous research to determine which cells show changes in the activation of genes related to cytokines after MLV or BBB damage. The scientists will then compare cognitively unimpaired mice to genetically engineered Alzheimer’s-like mice with and without damaged MLVs to see how this affects Alzheimer’s brain changes, learning and memory, and BBB function. Finally, Dr. Storck’s team will see how improving MLV function in cognitively unimpaired mice and genetically engineered Alzheimer’s-like mice affects these same measures. The researchers propose that enhanced MLV function may provide a protective effect to Alzheimer’s-like brain changes.
Impact
This study may help us understand how MLV and BBB function collectively influence brain changes seen in aging and in Alzheimer’s. These results may highlight potential therapeutic interventions to maintain brain health throughout aging and possibly prevent brain changes seen in Alzheimer’s.