Washington DC, June 22: Researchers in Spain and Switzerland have identified an experimental molecule that may help restore the brain’s natural defence system against Alzheimer’s disease, offering a potential new approach for future treatments.
The molecule, known as OLE, was found to reprogram microglia — the immune cells of the brain — enabling them to regain their ability to respond to harmful protein deposits associated with the disease. The findings were published in the journal Cell Death and Disease.
The study was led by Jose Vicente Sanchez Mut of the Institute for Neurosciences (IN-CSIC-UMH) in Spain and Johannes Graff of the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland.
Researchers found that OLE, a molecule produced by the PM20D1 gene, helped microglia move toward beta-amyloid plaques, which are considered a hallmark of Alzheimer’s disease. The treated immune cells formed protective barriers around the plaques, limiting their interaction with nearby neurons and reducing damage to brain tissue.
According to the researchers, microglia gradually lose their protective functions during the progression of Alzheimer’s disease, contributing to neuronal damage. The study suggests that OLE may reverse some of these changes by restoring the cells’ protective role.
To evaluate the compound, scientists first used genetically modified Caenorhabditis elegans worms that produce beta-amyloid proteins. Treatment with OLE reduced protein accumulation and improved movement in the animals.
The research team also tested the molecule in mouse models of Alzheimer’s disease. Mice treated with OLE for three months performed better in memory tests and showed fewer beta-amyloid plaques in the brain compared to untreated animals.
Further analysis of thousands of individual brain cells revealed that microglia were the cells most strongly affected by the treatment. Researchers observed that OLE activated pathways associated with the clearance of beta-amyloid deposits and improved the cells’ ability to migrate toward and contain the plaques.
Laboratory experiments involving cultured brain cells produced similar results, with treated microglia showing increased activity against beta-amyloid deposits. In separate neuronal cell studies, OLE also improved cell survival under conditions designed to mimic Alzheimer’s disease.
The findings have been covered by two European patents, including one held by the Spanish National Research Council (CSIC). Researchers said the patents support future efforts to develop therapeutic applications based on the discovery.
While the results are encouraging, the researchers noted that further studies and clinical trials will be required to determine the safety and effectiveness of OLE in human patients.