The investigators are working together to understand the role that innate immunity — the body’s defense system — plays in Alzheimer’s disease, a disorder of dementia that is rapidly increasing as the population ages.
The teams are focused on uncovering and manipulating the key molecular players in innate immunity with an ultimate goal of developing novel therapies for Alzheimer’s disease, says neurologist and neuroscientist Nilufer Ertekin-Taner, M.D., Ph.D., one of the grant’s two principal investigators from Mayo Clinic in Florida. The other is Steven Younkin, M.D., Ph.D.
“When activated, human innate immunity results in inflammation, and previous research on this response to development of Alzheimer’s disease has been contradictory because no one has yet looked at the whole picture of this effect over time,” says Dr. Ertekin-Taner. “It may be that an initial inflammatory response is beneficial, perhaps even protective, but a lengthy response to toxic proteins acts to kill healthy neurons.
“Our goal is to understand exactly if and when an innate immune response is good, and when it is bad, and to identify drug targets that enhance this protective effect and shut down the destructive side of this inflammation.”
To do that, the study’s leaders — which include Todd Golde, M.D., Ph.D., director for Translational Research in Neurodegenerative Disease at the University of Florida, and Nathan Price, Ph.D., from the Institute for Systems Biology — have designed a systems level approach.
“We want to look at all the different components together,” Dr. Ertekin-Taner explains. For example, using brain samples of Alzheimer’s disease patients from Mayo Clinic’s brain bank directed by Dennis Dickson, M.D., and clinical samples from collaborators in Neurology, Dr. Ertekin-Taner and Dr. Younkin will generate biological information. This will include identification of key genes and RNA transcripts involved in the innate immune response to the disease.
Dr. Golde, a former chair of the Department of Neuroscience at Mayo Clinic, will use animal models of Alzheimer’s disease to find similar expression data; he will also test findings from the Mayo researchers in the animals. Dr. Price will employ advanced computational methods to synthesize data generated by the teams to identify key molecules involved in this pathway. Dr. Golde will then test these results in the animal models, and see what happens when molecular targets are manipulated with novel agents.
“This grant is a beautiful example of bringing together large data and expertise from different groups into a single goal to really understand key aspects of this important pathway,” Dr. Ertekin-Taner says. “We have great hope for such a novel and cutting-edge approach like this, and can’t wait to get started.”
The study is supported by National Institutes of Health grant 1U01AG046139-01.
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