Researchers from Spain and Switzerland identify molecule OLE that restores microglia to a protective state, reducing toxic plaques and improving memory in animal models.
Scientists from Spain and Switzerland have identified a naturally occurring molecule that may restore the brain’s own immune defences against Alzheimer’s disease, offering a potentially new direction in the search for effective treatments for a condition that affects more than 55 million people worldwide.
The compound, known as OLE and derived from the PM20D1 gene, was found to reprogram microglia — the brain’s resident immune cells — back into a protective state. In animal studies, the treatment led to a measurable reduction in toxic beta-amyloid plaques and improved performance on memory tests. The findings were published in the peer-reviewed journal Cell Death and Disease.
The research was led by José Vicente Sánchez Mut of the Institute for Neurosciences, a joint centre of the Spanish National Research Council (CSIC) and Miguel Hernández University of Elche, alongside Johannes Gräff of the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland.
What microglia do — and why they fail
Microglia are specialised immune cells that reside permanently in the brain, tasked with identifying and clearing harmful deposits, including the beta-amyloid protein fragments that are a hallmark of Alzheimer’s disease. As the condition progresses, microglia undergo a functional deterioration — losing their capacity to remove plaques and, in later stages, contributing actively to neuroinflammation and neuronal damage.
The OLE molecule was found to reverse this process. Following treatment, microglia migrated toward beta-amyloid plaques, formed a containment barrier around them, and reduced their toxic contact with surrounding neurons. Single-cell analysis of thousands of individual brain cells confirmed that microglia were the cell type most strongly affected by the treatment.
“One of the most significant findings is that we have identified a molecule capable of restoring microglia’s protective function. In Alzheimer’s disease, these cells become progressively impaired. Our results suggest that this process can be reversed,” said Sánchez Mut.
Testing across multiple models
The researchers tested OLE first in genetically modified Caenorhabditis elegans worms, which develop beta-amyloid-related damage rapidly. The compound reduced protein aggregation and improved motor function. Subsequent trials in mouse models, conducted over three months, confirmed a reduction in plaque burden and improved memory performance. Laboratory cell culture experiments further indicated that OLE may directly protect neurons, independent of its effect on microglia.
