Researchers in Spain and Switzerland report that an experimental molecule called OLE helped restore protective behavior in the brain’s immune cells in animal models of Alzheimer’s disease, reducing amyloid-related pathology and improving performance on memory and movement tests.
Researchers in Spain and Switzerland say they have identified an experimental molecule, dubbed OLE, that can push microglia — the brain’s resident immune cells — back toward a more protective state in models of Alzheimer’s disease.
In a report published in Cell Death & Disease, the team said OLE helped microglia move toward beta-amyloid plaques and surround them, forming a barrier that limited contact between plaques and nearby neurons. The researchers reported that this was associated with smaller plaques and reduced harmful effects in the studied models.
“One of the most significant findings is that we have identified a molecule capable of restoring microglia's protective function,” said José Vicente Sánchez Mut, one of the study leaders.
The work was led by Sánchez Mut at the Institute for Neurosciences (a joint center of Spain’s CSIC and Miguel Hernández University of Elche) and Johannes Gräff at the École Polytechnique Fédérale de Lausanne (EPFL).
To test the approach, the researchers first used genetically modified C. elegans worms engineered to produce beta-amyloid. They reported that OLE reduced the buildup of protein aggregates and improved the worms’ movement. The team then administered OLE to mouse models of Alzheimer’s disease for three months and said treated animals performed better on memory tests and had fewer beta-amyloid plaques than untreated mice.
Using single-cell analyses of thousands of brain cells, the researchers said microglia showed the strongest response to OLE.
“Single-cell analysis allowed us to determine that microglia were the cells that responded most strongly to the treatment,” said Victoria Pozzi, the study’s first author.
The researchers also reported supportive results in cell-culture experiments, including improved microglial movement toward amyloid deposits and improved neuronal survival under Alzheimer’s-like conditions.
The team said the findings are covered by two European patents, including one owned by the CSIC, and that the research was supported by a mix of Swiss and Spanish public funding and foundations, including the Dementia Research Switzerland–Synapsis Foundation and the Pasqual Maragall Foundation’s researchers program, as well as agencies and programs in Spain and Switzerland and European Union-linked funds.
