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AsianScientist (Oct. 27, 2026) –Blocking an immune signalling pathway in the brain can help restore the function of the brain’s immune cells and calm overactive neurons in a mouse model of Alzheimer’s disease, found a study led by Sungkyunkwan University (SKKU), South Korea. The findings were published in Science Advances.

Alzheimer’s disease, known for memory loss and cognitive decline, is marked by clumps of beta-amyloid protein, called plaques, building up between nerve cells. The few approved treatments use antibodies to help clear these plaques. Researchers are also exploring a different approach borrowed from cancer immunotherapy: blocking PD-1 and PD-L1, two proteins that act as brakes on immune cells. A 2016 study found that blocking PD-1 reduced amyloid plaques and improved memory in Alzheimer’s mice. But how releasing this brake affects the brain’s own immune cells has remained unclear.

The SKKU team, working with Yonsei University and the biotech company IMNEWRUN, focused on two types of brain immune cells. Microglia, the brain’s resident immune cells, keep the brain’s environment stable and respond to damage. Astrocytes support both microglia and neurons. In Alzheimer’s, microglia stop responding properly, and neurons become overactive, disrupting brain networks.

Normally, the PD-1/PD-L1 brake stops immune cells from overreacting. But in Alzheimer’s, PD-1 and PD-L1 levels rise in glial cells in both mice and patients. The researchers suspected the brake was being pressed too hard, leaving microglia too sluggish to do their job.

To test this, they injected an antibody that blocks PD-L1 directly into the brains of mice, which were engineered to develop Alzheimer’s-like plaques. Using a fluorescence imaging technique called two-photon microscopy, they watched living brain cells in real time.

With the brake released, microglia once again extended toward sites of damage and produced more P2RY12, a marker of healthy microglia. Neurons stopped firing abnormally and the toxic amyloid plaques were reduced. Removing PD-L1 from astrocytes alone had the same effect, suggesting these support cells are the ones applying the brake.

Minah Suh, the study’s corresponding author, said the findings suggest that precisely modulating immune proteins within the brain could offer a new therapeutic strategy for Alzheimer’s.

The effects were stronger when the antibody was injected directly into the brain than when it was given through the body, which could be a hurdle for treatment, since brain injections carry risks. The experiments were also done in anaesthetised mice. Future studies in awake, behaving animals could show whether the treatment affects memory and behaviour. Still, the findings point to a shift in how Alzheimer’s could be tackled: not only by clearing plaques, but by helping the brain’s own immune cells do their job again.

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Source: Sungkyunkwan University ; Image:PeopleImages/shutterstock

The study can be found at: 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).