Targeting brain cleaning gene could help treat or prevent Alzheimer's

A gene responsible for compacting trash inside the brain appears to be a key player in Alzheimer's disease, and doctors may be able to target it to better treat or help prevent the devastating condition, new UVA Health research suggests.

Alzheimer's development

Alzheimer's affects more than 6 million Americans. It is a progressive disease that worsens over time, robbing people of their memories to the point they can forget their own children. It is the sixth-leading cause of death in the United States.

The development of Alzheimer's is accompanied by the buildup of sticky clusters of proteins inside the brain known as amyloid-beta plaques, as well as twisted tangles of tau proteins. Recent research has shown that the immune system – specifically microglia – may be playing a central role in this.

When functioning properly, microglia form protective barriers around the amyloid-beta plaques and compact them down as small as possible to minimize the harm they can cause. But Lukens' new research suggests that faulty or ineffective variants of the gene can leave the brain inadequately defended. In lab mice, this impaired the microglia, caused amyloid-beta buildup, harmed nerve cells called neurons and sent the mice into cognitive decline.

Based on their results, the scientists suspect that doctors may be able to develop ways to target the gene or the microglia in the brain to help slow or prevent the development of Alzheimer's.

Lukens' Harrison Family Translational Research Center in Alzheimer's and Neurodegenerative Diseases is part of UVA's new Paul and Diane Manning Institute of Biotechnology. The institute has been launched to accelerate the development of new drugs and treatments for complex diseases based on UVA's cutting-edge biomedical research discoveries.

Lukens is also part of UVA's Center for Brain Immunology and Glia (BIG Center).

Findings published

Lukens and his colleagues have published their new findings in the Journal of Experimental Medicine. The research team consisted of Adeline E. Walsh, Benjamin A. Davis, Joshua D. Samuels, William A. Mills III, Jessica M. Thanos, Alexis M. Johnson, Katelyn A. Moore, Michael A. Puchalski, Eric J, Steacy, Benjamin W. Wendell, Amélie Daugherty-Lopès, Adrian A. Shimpi, Ukpong B. Eyo and Lukens. The scientists have no financial interest in the work.

Davis is a fourth-year biology student at UVA. "I think that undergraduate research develops a kind of critical thinking that is difficult to cultivate inside a classroom," he said. "My experience with research has taught me to approach questions systematically and never assume there will be a clear answer. As I prepare to apply to medical school, I know these experiences will shape how I approach clinical care and the broader field of science."

The research was supported by the National Institutes of Health's National Institute on Aging, grants R01AG071996, R01AG087406, RF1AG078684 and R01AG086344; the Cure Alzheimer's Fund; the Owens Family Foundation; the Harrison Family Foundation; the Rick Sharp Foundation; and the Steven A Newman AD Award.

Source:

University of Virginia Health System

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