University of Kentucky
2009 Zenith Fellow
Understanding the Role of Brain Inflammation in Alzheimer's Disease
Dr. Linda Van Eldik is a leader in field of neuroimmunology, which focuses on the link between the immune system and the brain. Immune cells in the brain called microglia perform many important functions, but they can also promote brain inflammation, a hallmark of Alzheimer's and other neurodegenerative diseases. Recent evidence also suggests brain inflammation may underlie the connection between traumatic brain injury (TBI) and later risk for developing dementia. Though the exact mechanisms remain unknown, Dr. Van Eldik and colleagues hypothesize that TBI may cause microglia to produce high levels of inflammatory molecules, which in turn can promote other brain changes that lead to Alzheimer's disease. Dr. Van Eldik has shown that brain injury in Alzheimer's-like mice leads to increased neuroinflammation, cognitive decline and higher levels of beta-amyloid, a protein fragment closely linked with Alzheimer's. Traumatic brain injury may have a similar effect in humans at risk of Alzheimer's disease, a linkage that requires future investigation. These studies give us new insight into how Alzheimer's disease might be initiated and help us understand how the brain's immune system can have both negative and positive effects.
Since her Zenith award in 2009, Dr. Van Eldik has received over $12 million in National Institutes of Health (NIH) funding related to Alzheimer's and other dementias research. Recently she was awarded an Alzheimer's Association Part the Cloud Translational Research grant for $1 million to support a Phase I human clinical trial of an experimental drug (MW189) designed to reduce brain inflammation. This novel drug has been shown to target microglia and specifically prevent overproduction of molecules called proinflammatory cytokines induced by injury or disease. The mechanism is different than other drug mechanisms that suppress normal cytokine levels, which can have negative effects. The clinical trial of MW189 will test the safety of different doses of the drug in healthy volunteers. If successful, the drug will advance to future clinical trials in individuals with traumatic brain injury or Alzheimer's disease to determine if it can effectively inhibit brain inflammation and improve cognitive function.
Dr. Van Eldik's research is providing key insights into neuroinflammatory mechanisms. Her research will help pave the way toward development of novel therapeutics designed to harness the brain's immune system to reduce damage while allowing normal and beneficial functions to remain intact. Because neuroinflammation is involved in brain injury and many neurodegenerative diseases, therapies that successfully target this process could have broad implications for treating Alzheimer's and a large number of related disorders.