OLE Molecule Reprograms Brain Cells for Alzheimer's

Researchers led by José Vicente Sánchez Mut at the Institute for Neurosciences (IN) and Johannes Gräff at the École Polytechnique Fédérale de Lausanne (EPFL) have identified an experimental molecule, Ole, capable of 'reprogramming' the brain's immune cells (microglia) to restore their protective function against Alzheimer's disease. The study, published in Cell Death and Disease, demonstrates that Ole helps microglia enclose and contain beta-amyloid plaques, reducing their size and toxicity. In animal models, treatment with Ole improved cognitive performance in memory tests and reduced beta-amyloid plaques. The molecule, derived from the PM20D1 gene, restores microglia to a more protective state, enabling them to move towards and encapsulate plaques, limiting their interaction with neurons. Single-cell analysis confirmed microglia as the primary responders to Ole, activating mechanisms for beta-amyloid clearance. In vitro experiments also showed enhanced microglial chemotaxis and degradative capacity, along with increased neuronal survival under stress. The findings are protected by two European patents, one held by the Spain — Spanish National Research Council (CSIC), reinforcing the translational potential for future therapeutic development. The research received extensive funding from various national and international organizations.