Inflammatory Driver

Study reveals the role of the messenger IL-12 in Alzheimer’s disease and suggests a potential approach for treatment

Co-cultures consisting of neurons that form nerve fibers (pink) and oligodendrocytes that wrap these nerve fibers with myelin (white). The cell nuclei are stained blue. Source: Charité | AG Heppner

“Neuroinflammation” is a collective term for inflammatory processes caused by the brain’s immune system that are increasingly becoming the focus of Alzheimer’s research. A study has now unravelled the role of the messenger “IL-12” in this context: In Alzheimer’s disease, this molecular mediator of inflammation is released by the “microglia” – the brain’s immune cells – thereby fuelling the disease process, as the latest research shows. The study involved a team led by Frank Heppner, a scientist at DZNE’s Berlin site and at the Charité – Universitätsmedizin Berlin, as well as experts from Max Delbrück Center.

According to the current findings, the signaling molecule “Interleukin-12“ (IL-12), previously known primarily for its role in autoimmune diseases like Crohn’s disease, appears to play a pivotal role in Alzheimer’s as it damages two key types of brain cells: “oligodendrocytes”, which normally produce the fatty insulating layer around nerve fibers essential for rapid signal transmission, as well as so-called “interneurons”.

An approach to combination therapy?

“We now have a highly detailed picture of this mechanism. The only remaining question is which cell type IL-12 impacts first – oligodendrocytes, interneurons, or both simultaneously,” says Heppner. The study has immediate implications as there are already drugs on the market that block IL-12. Thus, the researchers hope that clinicians will build on their findings and initiate clinical trials. “If these drugs prove effective, they would be a new arrow in the quiver. Alzheimer’s doesn’t just have one cause. One axis of the disease is also controlled by the immune system, at least in some patients. Slowing neurodegeneration will require combination therapy,” Heppner emphasizes. Such an approach could start early in the disease process, as IL-12 can be measured in blood or cerebrospinal fluid, he adds.

More information: Press release by Charité and Max Delbrück Center

Original publication
Interleukin-12 signaling drives Alzheimer’s disease pathology through disrupting neuronal and oligodendrocyte homeostasis.
Schneeberger et al.
Nature Aging (2025).
DOI: 10.1038/s43587-025-00816-2

_{April 2025}