Scientists Block Key Molecule to Protect Mice From Alzheimer’s

Scientists at the University of Virginia have discovered that blocking a single immune molecule called STING can prevent the cognitive decline and brain damage seen in Alzheimer’s disease.

The research, published in Alzheimer’s & Dementia, reveals how the brain’s own defense system may actually drive the formation of toxic plaques that destroy memory and thinking skills.

The findings challenge conventional thinking about Alzheimer’s causes. Rather than focusing solely on the buildup of amyloid plaques, the research suggests these plaques form partly because the immune system goes haywire while trying to repair DNA damage that naturally occurs as we age.

DNA Damage Triggers Brain Inflammation

“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, PhD, 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 stands for stimulator of interferon genes. Think of it as a cellular alarm system that normally helps clear out viruses and damaged cells. But in Alzheimer’s brains, this alarm never stops ringing.

The researchers used mice genetically engineered to develop Alzheimer’s-like symptoms. When they deleted the STING gene from these mice, the results were striking. The animals maintained better memory and learning abilities compared to their unmodified counterparts.

Multiple Benefits From Single Target

What makes STING particularly attractive as a treatment target is its broad impact on Alzheimer’s pathology. The research team found that blocking STING activity produced several beneficial effects:

• Reduced formation of amyloid plaques by up to 40% in brain regions
• Decreased tau protein tangles that strangle neurons
• Protected neurons from toxic damage around plaques
• Improved spatial learning and memory performance
• Reduced brain inflammation and oxidative stress

Using advanced single-cell RNA sequencing, the researchers discovered that STING deletion fundamentally rewired gene expression in brain cells. Microglia—the brain’s resident immune cells—shifted from a hyperactive, disease-promoting state to a more balanced, protective profile.

Beyond Traditional Alzheimer’s Targets

“We found that removing STING dampened microglial activation around amyloid plaques, protected nearby neurons from damage and improved memory function in Alzheimer’s model mice,” said researcher Jessica Thanos, part of UVA’s Department of Neuroscience and Center for Brain Immunology and Glia. “Together, these findings suggest that STING drives detrimental immune responses in the brain that exacerbate neuronal damage and contribute to cognitive decline in Alzheimer’s disease.”

The study revealed something particularly intriguing that wasn’t highlighted in the press materials: STING-deficient mice showed increased expression of MEF2C, a gene crucial for neuronal survival that’s also a known Alzheimer’s risk factor. This suggests STING may suppress protective pathways while promoting harmful ones.

Most current Alzheimer’s treatments target individual symptoms or specific disease stages. STING inhibition appears different—it simultaneously attacks multiple disease mechanisms while potentially strengthening the brain’s natural defenses.

Broader Implications for Brain Disease

The implications extend beyond Alzheimer’s. STING appears to play similar destructive roles in Parkinson’s disease, ALS, and other neurodegenerative conditions. This raises the possibility that STING inhibitors could become broad-spectrum treatments for multiple brain diseases.

However, translating these findings into human treatments faces significant challenges. STING serves important functions in fighting cancer and infections. Any therapeutic approach would need to carefully balance immune suppression against these protective roles.

The researchers are particularly interested in understanding which specific cell types need STING blockade for maximum benefit. This could enable more targeted therapies that preserve beneficial immune functions while blocking harmful brain inflammation.

Path Forward

With over 7 million Americans living with Alzheimer’s—a number projected to exceed 13 million by 2050—the urgency for new treatments continues to grow. Current FDA-approved medications provide modest benefits at best, and several high-profile drug candidates have failed in clinical trials.

“Our hope is that this work moves us close 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 research was supported by the National Institutes of Health, the Alzheimer’s Association, and several private foundations. The team plans to investigate exactly how DNA damage accumulation triggers STING activation and whether existing STING inhibitors might be repurposed for brain diseases.

Could blocking one immune molecule hold the key to protecting millions of aging brains? These early results suggest the answer might be yes—but the real test will come in human clinical trials still years away.