A new way of thinking about Alzheimer’s disease has led to a discovery with the potential to stop the cognitive decline seen in patients with Alzheimer’s and other neurodegenerative diseases, according to University of Virginia researchers.

The scientists are investigating whether Alzheimer’s may result in part from the immune system’s faulty attempt to repair DNA damage in the brain.

Researchers at the UVA School of Medicine found blocking a brain-defense molecule in mice prevented memory loss and other signs of mental decline. The molecule, called STING, triggers the buildup of the toxic plaques and tangles linked to the disease. 

When researchers blocked STING, the mice were protected from memory loss and other signs of mental decline.

“Our findings demonstrate that the DNA damage that naturally accumulates during aging triggers STING-mediated brain inflammation and neuronal damage in Alzheimer’s disease,” said researcher John Lukens, director of UVA’s Harrison Family Translational Research Center in Alzheimer’s and Neurodegenerative Diseases. “These results help to explain why aging is associated with increased Alzheimer’s risk and uncover a novel pathway to target in the treatment of neurodegenerative diseases.”

STING, a key part of the brain’s immune system, may also contribute to Parkinson’s, ALS, dementia and other memory-related diseases. Targeting STING could lead to treatments benefiting patients with these serious conditions.

Alarming Trends in Alzheimer’s
Alzheimer’s is a growing crisis, affecting more than 7 million Americans today – a number that could surpass 13 million by 2050. Researchers are racing to better understand and treat the disease.

While the causes of Alzheimer’s remain unclear, scientists are increasingly recognizing the immune system’s role in the disease. STING, an immune molecule helping to clear viruses and damaged cells, is part of that response. Though it defends the brain, STING can become overactive, triggering inflammation and tissue damage. 

Curious about its role in Alzheimer’s, Lukens and his team blocked STING in lab mice. The result was reduced plaque buildup, changes in immune cell behavior and shifts in gene activity linked to the disease.

Promising Treatment Target
Although scientists have explored other molecules linked to Alzheimer’s, UVA Health researchers say STING stands out as a strong target for new treatments. Blocking STING appears to slow both plaque buildup and tangle formation – the two main hallmarks of Alzheimer’s. In contrast, other molecules play a more limited role and can be targeted only at specific stages of progression.

“We are only beginning to understand the complex role of innate immune activation in the brain, and this is especially true in both normal and pathological aging,” said researcher Jessica Thanos, part of UVA’s Department of Neuroscience and its Center for Brain Immunology and Glia. “If we can pinpoint which cells and signals sustain that activation, we will be in a much better position to intervene effectively in disease.”

While Lukens’ pioneering research has opened new doors in the fight against Alzheimer’s, more work is needed to translate the findings into treatments. To avoid unwanted side effects, scientists must better understand how STING functions in the body, including its role in the immune response to cancer.

“Our hope is that this work moves us closer to finding safer and more effective ways to protect the aging brain, as there is an urgent need for treatments that can slow or prevent neuronal damage in Alzheimer’s,” Lukens said. “Shedding light on how STING contributes to that damage may help us target similar molecules and ultimately develop effective disease-modifying treatments.”

The National Institute on Aging, the Alzheimer’s Association, the Cure Alzheimer’s Fund, the Owens Family Foundation and the Harrison Family Foundation supported UVA’s research.

Source: https://news.virginia.edu/content/uva-study-brains-defense-system-may-drive-alzheimers