The National Institutes of Health has awarded the Oklahoma Medical Research Foundation a five-year, $3.7 million grant to study immune reactions in the brain that may lead to conditions like Alzheimer’s.
Ultimately, the grant could lead to a new medication that slows or even stops the immune response.
Bill Freeman, Ph.D., the principal investigator on the grant, will lead a study that targets the brain’s dedicated immune cells, called microglia. He’ll also look at a surveillance network that’s constantly on alert for potential threats to the body – and also appears to be implicated in Alzheimer’s and other brain diseases associated with aging.
The surveillance network exists throughout our bodies and is particularly crucial following organ transplantation. Until roughly a decade ago, scientists didn’t think it existed in the brain, Freeman said.
“Turns out it is there, and for reasons we don’t quite understand yet, it becomes more active with aging, especially with conditions like Alzheimer’s,” he said. “This grant is about trying to figure out whether this is happening as a cause or as a symptom of aging and these diseases.”
Freeman hypothesizes that in Alzheimer’s, this surveillance network initially is protective. But at some point, its full-alert mode may become counterproductive and actually worsen Alzheimer’s by altering the function of the brain’s immune cells.
If proven true, it would join a list of biological processes that can help the body – only to go on too long and end up causing damage. “When that happens, the cure becomes worse than the disease,” Freeman said.
As part of the new grant, one of Freeman’s collaborators, OMRF scientist Heather Rice, Ph.D., will also investigate changes in amyloid beta protein, which is found in the brain and spinal cord. In Alzheimer’s, the protein forms clumps, or plaques, which can be toxic to brain cells.
“The buildup of these plaques is a hallmark of Alzheimer’s, so I’ll be studying what changes occur in these proteins when the brain’s surveillance network becomes hyperactive,” Rice said.
Freeman said that experiments funded by the new grant should cast new light on a “previously underappreciated” part of the immune system.
“Longer term,” Freeman said, “we hope this research will lead us toward a new therapeutic approach to modulate the immune response in the brain – one that can maintain brain health into later years and slow progression of neurodegenerative diseases.”
The grant, RF1AG085573-01A1, was awarded by the National Institute on Aging, part of the NIH.
