Scientists have identified a method to restore parts of the brain’s immune response and reduce abnormal nerve-cell activity associated with Alzheimer’s disease. The study was conducted by Professor Minah Suh from Sungkyunkwan University’s department of biomedical engineering in partnership with IMNEWRUN biotechnology and Professor Ho-Keun Kwon’s team at Yonsei University College of Medicine.
Microglia and Immune Response
The focus was on the brain’s immune cells, known as microglia, which typically serve as the brain’s initial responders. They detect damage and sustain a healthy environment in the brain. In Alzheimer’s disease, this immune response is disrupted, leading to increased nerve cell activity.
Key Proteins: PD-1 and PD-L1
The study, published in Science Advances, links these disruptions to immune-regulating proteins PD-1 and PD-L1. Mice modeled on Alzheimer’s disease showed elevated levels of PD-1 in microglia and PD-L1 in astrocytes, which maintain brain health.
The research adds to the evidence that the immune system plays a significant role in Alzheimer’s disease and dementia.
Research Process and Findings
Researchers directly administered a PD-L1 blocking antibody into the brains of model mice, using advanced microscopy to observe brain cells. The microglia regained their ability to respond to damaged areas and neuronal activity was reduced.
One of the clearest pieces of evidence that the immune system is involved is that individuals who receive the shingles vaccine are less likely to develop dementia.
Dr. John Showalter, from Linus Health, noted this reinforces the role of immune mechanisms in Alzheimer’s, potentially stimulating more immune-focused research.
Implications and Future Research
The study found stronger effects when PD-L1 was altered in the brain, suggesting that immune signaling disruptions might affect brain responses to damage. However, blocking PD-L1 does not yet offer a treatment for humans. Conducted on mice with an Alzheimer’s-like condition, this research provides a promising approach rather than a confirmed treatment.
The challenges lie in delivering antibodies safely to humans. Dr. Showalter highlighted the risk in injecting medications directly into brain and spinal fluid. More research is needed to confirm similar 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.
Leave a Reply