Daijiworld Media Network - Madrid
Madrid, Jun 20: Scientists in Spain and Switzerland have identified a new experimental molecule that could help restore the brain’s natural defence system against Alzheimer’s disease, offering a potential new approach for future therapies.
The molecule, named OLE, was found to “reprogram” microglia — the immune cells of the brain — helping them regain their protective functions. Researchers found that the treatment reduced the buildup of toxic beta-amyloid plaques and improved memory performance in Alzheimer’s disease models.
The study was led by Jose Vicente Sanchez Mut from the Institute for Neurosciences (IN), a joint centre of the Spanish National Research Council (CSIC) and Miguel Hernandez University of Elche (UMH), along with Johannes Graff of the École Polytechnique Federale de Lausanne (EPFL). The findings were published in the journal Cell Death and Disease.
Researchers found that OLE helps microglia move towards beta-amyloid plaques, surround them and reduce their harmful impact on nearby brain cells. In animal experiments, the treatment also improved performance in memory-related tests.
Alzheimer’s disease is characterised by the accumulation of beta-amyloid plaques in the brain. Normally, microglia help clear these harmful deposits, but as the disease progresses, these immune cells lose their effectiveness and may contribute to further brain damage.
The researchers discovered that OLE, a molecule produced by the PM20D1 gene, can restore microglia to a more protective state. After treatment, the cells became more active in clearing plaques and formed protective barriers around them, reducing damage to surrounding neurons.
“One of the most significant findings is that we have identified a molecule capable of restoring microglia’s protective function,” Sanchez Mut said, adding that the findings suggest the impaired state of these cells in Alzheimer’s could potentially be reversed.
To test the molecule, scientists used genetically modified worms and mouse models of Alzheimer’s disease.
In worms producing beta-amyloid, OLE reduced toxic protein buildup and improved movement. In mice treated with the molecule for three months, researchers observed improved memory performance and fewer beta-amyloid plaques compared to untreated animals.
Further analysis using single-cell studies showed that microglia were the cells most strongly affected by OLE. The treatment activated pathways linked to plaque removal and helped the cells move towards damaged areas.
“Single-cell analysis allowed us to determine that microglia were the cells that responded most strongly to the treatment,” said Victoria Pozzi, the first author of the study.
Additional laboratory tests showed that microglia treated with OLE were more effective at removing beta-amyloid deposits. Experiments involving neurons also indicated that OLE could improve cell survival under Alzheimer’s-like conditions.
The discovery has been protected through two European patents, including one owned by CSIC, strengthening its potential for future development into therapeutic applications.
Researchers said further studies will be needed before the molecule can be considered for human treatment, but the findings open a promising new direction in Alzheimer’s research.