Researchers from Spain and Switzerland have found a new molecule that may help the brain protect itself from Alzheimer’s disease. The compound is called OLE. It seems to change brain immune cells called microglia, giving them back some of their protective powers.
The study was led by José Vicente Sánchez Mut from the Institute for Neurosciences, a partnership between the Spanish National Research Council and Miguel Hernández University of Elche, together with Johannes Gräff from EPFL in Switzerland. Their results were published in the journal Cell Death and Disease.
OLE helps microglia gather around beta‑amyloid plaques. This makes the plaques smaller and less harmful. In animal tests, the treated subjects also performed better on memory tasks.
How OLE Works Against Alzheimer’s
Alzheimer’s is marked by the build‑up of beta‑amyloid plaques. Normally, microglia clean up these toxic pieces. Over time, the cells become weaker and can even damage brain cells.
OLE is a molecule that comes from the PM20D1 gene. It pushes microglia back into a protective state. After receiving OLE, the cells move toward plaques, surround them, and create a barrier that keeps the plaques away from nearby neurons. This reduces the damage caused by the plaques.
“We found a molecule that can bring back the protective role of microglia,” says Sánchez Mut. “In Alzheimer’s, these cells lose function, but OLE can reverse that loss.”
Testing OLE in Worms and Mice
First, the scientists used special worms (C. elegans) that make beta‑amyloid. These worms develop damage quickly, making them useful for testing. Giving the worms OLE lowered the amount of protein clumps and helped them move better.
Next, they treated mouse models of Alzheimer’s with OLE for three months. The mice that received the drug remembered better and had fewer plaques compared with untreated mice.
Microglia Respond the Most
The team examined thousands of individual brain cells to see which ones changed the most. Microglia showed the strongest response to OLE.
After OLE exposure, microglia turned on pathways that clear beta‑amyloid. They moved toward plaques and kept them contained.
Similar results appeared in cell‑culture experiments. Microglia treated with OLE moved toward deposits more efficiently and helped remove them. Neurons exposed to Alzheimer‑like conditions also survived better when OLE was present.
What This Means for Future Treatments
The discovery is covered by two European patents, one owned by the CSIC. This helps protect the idea and supports future work to turn OLE into a medicine.
The research was funded by several organizations, including Dementia Research Switzerland, the Pasqual Maragall Foundation, the Spanish Ministry of Science, and the European Research Council, among others.