Researchers have identified a method to restore parts of the brain’s immune function and decrease abnormal nerve-cell activity linked to Alzheimer’s disease. This study was spearheaded by Professor Minah Suh from the department of biomedical engineering at Sungkyunkwan University. Collaborators included the biotechnology company IMNEWRUN and Professor Ho-Keun Kwon’s team at Yonsei University College of Medicine. The focus was on the brain’s immune cells, known as microglia, which typically act as first responders in the brain. They detect damage and help maintain a healthy environment.

In Alzheimer’s disease, the function of microglia becomes impaired. This is accompanied by unusual nerve cell activity. The study, published in Science Advances, connects these disruptions to changes in two proteins that regulate the immune system, PD-1 and PD-L1. In mouse models of Alzheimer’s, researchers discovered increased PD-1 levels in microglia and elevated PD-L1 levels in astrocytes, which are cells that support the brain’s environment.

To determine the effects of these changes, scientists administered an antibody that blocks PD-L1 directly into the brains of mice with Alzheimer’s. Advanced microscopy allowed them to observe living brain cells. The results revealed that microglia regained proper function in responding to damaged areas, while the excessive neuronal activity lessened.

Dr. John Showalter, COO of Linus Health, commented on the research, noting that it bolsters the notion that the immune system plays a significant role in Alzheimer’s and dementia. He referenced the correlation between shingles vaccinations and lower dementia rates, highlighting how microglia might be directly involved in the disease process. He believes this will spark further interest in immune-focused research.

The study noted stronger effects when PD-L1 alterations were made directly in the brain rather than through the body. These findings suggest a connection between immune signaling disruptions, brain response to damage, and excessive neuron activity. Disrupted immune function might prevent microglia from maintaining a healthy brain environment.

The study aligns with a broader trend in Alzheimer’s research. Dr. Showalter pointed out that only about 25% of current randomized clinical trials for Alzheimer’s involve anti-amyloid and anti-tau drugs. In contrast, 16% involve anti-amyloid treatments, and 18% involve inflammation and immune-modifying therapies.

Although promising, the findings do not indicate a cure for Alzheimer’s disease in humans. The research was conducted on mice with an Alzheimer’s-like condition, representing a potential avenue to explore rather than a definitive treatment. Showalter emphasized that a significant challenge is delivering antibodies as a medication. Injecting directly into the brain’s fluid poses risks. Further research is necessary to explore these effects in humans.

Reference: Taeyoung Park et al., Targeting glial PD-1/PD-L1 restores microglial homeostasis and reduces neuronal hyperactivity in an Alzheimer’s disease model, Science Advances (2026). DOI: 10.1126/sciadv.adx0731