New discovery reveals immune molecule’s role in Alzheimer’s disease

A new way to think about Alzheimer’s disease has resulted in a discovery that could be the key to stop the cognitive decline that is seen at Alzheimer’s and other neurodegenerative diseases.

Scientists from the University of Virginia School of Medicine have investigated the possibility that Alzheimer’s, at least partly, is caused by the quirky attempts of the immune system to repair DNA damage in the brain. Their research shows that an immune molecule called Sting drives the formation of the harmful plaques and protein colors that is responsible for Alzheimer’s. Blocking the molecule protected lab mice of mental decline, the researchers say.

An important player in the brain immune system, Sting can also make an important contribution to Parkinson’s disease, Amyotrophe lateral sclerosis (ALS or Lou Gehrig’s disease), dementia and other memory -dependent disorders. This means that the development of treatments to control its activity could have far-reaching benefits for many patients who are confronted with now-trying diagnoses.

Our findings show that the DNA damage that naturally accumulates during aging sting-mediated brain inflammation and neuronal damage in Alzheimer’s disease. These results help to explain why aging is associated with increased Alzheimer’s risk and discover a new route to target in the treatment of neurodegenerative diseases. “

John Lukens, PhD, researcher, director of Uva’s Harrison Family Translational Research Center in Alzheimer and Neurodegenerative Diseases

Alarming trends in Alzheimer

Alzheimer’s is a growing problem throughout the country and all over the world: more than 7 million Americans are already living with the condition, and that number could exceed 13 million by 2050. This has researchers who work frantically to find ways to better understand and treat the condition.

The causes of Alzheimer’s remain cloudy, but scientists are increasingly appreciating the role of the immune system in the development of the disease. Sting is part of that immune response; The molecule helps the clearance of viruses and stressed cells that accommodate DNA damage.

Although Sting is an important defender of the brain, it can also become hyperactive and cause harmful inflammation and tissue damage. Lukens and his team would have liked to determine which part it could play in Alzheimer’s. Blocking the activity of the molecule in lab mice, they found, helped in preventing the plaque formation of Alzheimer’s, changed the activity of immune cells called microglia and, among other things, the effect of important genes were transmitted.

“We have discovered that the removal of microglial activation fought around amyloid plaques, nearby neurons protected against damage and improved memory function in the model mice of Alzheimer,” said researcher Jessica Thanos, part of Uva’s Department of Neuroscience (Big Center and Center for Brain). “Together these findings suggest that Angel stimulates adverse immune response in the brain that worsen neuronal damage and contribute to the cognitive decline in Alzheimer’s disease.”

Promising treatment objective

Although scientists investigate other molecules that are important in Alzheimer’s, Sting provides a particularly attractive target for the development of new treatments, the UvA health researchers say. That is because blocking Sting both the structure of amyloid plaques and the development of TAU ties seems to be slowing down, the two leading candidates for the cause of Alzheimer’s. Other molecules lack that robust involvement and could also be aimed at very specific – and very limited – phases in the progression of the disease.

“We only start to understand the complex role of congenital immuneactivation in the brain, and this is especially the case in both normal and pathological aging,” said Thanos. “If we can indicate which cells and signals that support activation, we will be in a much better position to effectively intervene in the disease.”

Although the groundbreaking research by Lukens has opened new doors in the fight against Alzheimer’s, much more work has to be done to translate the findings into treatments. For example, scientists should better understand the role of sting in the body – as in the reaction of the immune system to cancer – to ensure that every new treatment does not cause undesirable side effects.

But those are the types of big questions that Lukens and his employees of the Harrison Family Translational Research Center would like to tackle as part of their efforts to accelerate new treatments and, ultimately, they hope, heal. (The center is part of Uva’s Paul and Diane Manning Institute of Biotechnology, now under construction in Fontaine Research Park.)

“Our hope is that this work brings us close to finding safer and more effective ways to protect the aging brain, because there is an urgent need for treatments that can delay or prevent neuronal damage at Alzheimer’s,” Lukens said. “Shorten how Sting contributes to that damage can help us to direct similar molecules and ultimately develop effective disease -modifying treatments.”

Findings published

The researchers have published their findings in Alzheimer & Dementia: The Journal of the Alzheimer’s Association. The research team consisted of Thanos, Olivia C. Campbell, Maureen N. Cowan, Katherine R. Bruch, Katelyn A. Moore, Hannah E. Ennerfelt, Nick R. Natale, Aman Mangalmurti, Nagaraj Kerur and Lukens. The scientists have no financial interest in the work.

The study was supported by the National Institutes of Health’s National Institute of Aging, Grants R01AG071996, R01AG087406 and RF1AG078684; The Alzheimer’s Association, Grant ADSF-21-816651; The Cure Alzheimer’s Fund; The Owens Family Foundation; And the Harrison Family Foundation.