Professor Minah Suh of the Department of Biomedical Engineering at Sungkyunkwan University, in collaboration with the biotechnology company IMNEWRUN and Professor Ho-Keun Kwon’s team at Yonsei University College of Medicine, has identified a mechanism by which modulating an immune protein in the brain can restore a disrupted brain immune environment and reduce abnormally elevated neuronal activity in an animal model of Alzheimer’s disease.
The findings provide scientific evidence supporting brain immune modulation as a potential therapeutic strategy for Alzheimer’s disease, a major neurodegenerative disorder. The study was published in the internationally renowned journal Science Advances.
Alzheimer’s disease is characterized not only by the accumulation of harmful protein deposits in the brain but also by dysfunction of cells that help maintain and protect the brain environment. In particular, microglia, the brain’s resident immune cells, rapidly respond to tissue damage and help maintain the surrounding environment. In Alzheimer’s disease, however, normal microglial responsiveness is impaired, while neurons can exhibit abnormally increased activity.
The research team focused on the immune-regulatory proteins PD-1 and PD-L1, which have been widely studied in the field of cancer immunotherapy. In Alzheimer’s disease model mice, the researchers found increased PD-1 expression in microglia and increased PD-L1 expression in astrocytes, which play an important role in maintaining the brain environment. The team then investigated how these changes in immune-regulatory signaling affect brain function.
To address this question, the researchers directly administered an antibody that blocks PD-L1 activity into the brains of Alzheimer’s disease model mice and observed the responses using advanced microscopy techniques that enable visualization of living brain cells.
The results showed that the impaired response of microglia to sites of tissue damage was restored following PD-L1 blockade, while the abnormally elevated activity of neurons was also reduced. The researchers further found that these effects were more pronounced when PD-L1 was directly modulated within the brain than when the antibody was administered systemically.
Professor Minah Suh said, “This study reveals that disruption of immune-regulatory signaling in the Alzheimer’s disease brain is closely associated with both impaired microglial function and abnormal neuronal activity. Our findings suggest that precisely modulating immune proteins within the brain could provide a new therapeutic strategy for Alzheimer’s disease.”
Taeyoung Park, an integrated M.S.–Ph.D. student at Sungkyunkwan University, served as the first author of the study, while Professors Minah Suh and Ho-Keun Kwon served as corresponding authors. The research was supported by the Korea Dementia Research Project, the Institute for Basic Science (IBS), and IMNEWRUN.