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2016 Grants - Scholtzova
CAA Treatment Via Innate Immunity Stimulation and MRI Detection in Primates
Henrieta Scholtzova, M.D., Ph.D.
New York University School of Medicine
New York, New York
2016 Alzheimer’s Association Research Grant (AARG)
Can a novel treatment that stimulates the brain’s immune system help prevent the harmful buildup of beta-amyloid in the brain?
Certain immune cells in the brain can become dysfunctional during Alzheimer’s disease, impairing their ability to clear harmful build-up of beta-amyloid. Beta-amyloid is a protein fragment that forms “plaques” in the brain – a hallmark of Alzheimer’s disease. Beta-amyloid can also accumulate in the brain’s blood vessels, a condition known as cerebral amyloid angiopathy (CAA) which may promote dementia. Molecules that stimulate immune cell activity may help promote clearance of beta-amyloid from the brain, but many of the recently developed drugs designed to do this have unwanted side effects including brain swelling and inflammation. Researchers are working to develop new therapies that can stimulate the immune system without causing these side effects.
In previous work, Henrieta Scholtzova, M.D., Ph.D., and colleagues found that a molecule that activates immune cells via a specific receptor called Toll-like receptor 9 (TLR9) can reduce beta-amyloid accumulation in the brains and blood vessels of Alzheimer’s-like mice without negative side effects. For their current studies, they will administer the treatment to non-human primates (squirrel monkeys) that naturally develop CAA. The researchers will measure the safety of the treatment and its impact on the animals’ cognitive function. They will also measure changes in beta-amyloid levels in the brain over time using magnetic resonance imaging (MRI). This will be the first study to use this specific molecule in aging squirrel monkeys with CAA – an important step in determining if this treatment may be safe for people with Alzheimer’s disease.
This study may provide a foundation for future clinical trials in humans using this novel treatment to help stimulate immune cells to clear beta-amyloid from the brain. If successful, these findings may offer critical data related its potential use as a safe and effective therapy to treat or prevent Alzheimer’s disease.