This Alzheimer’s drug activates the brain’s cleanup crew – microglia – to remove harmful amyloid plaques.
Published In: Nature Neuroscience
Date: November 2025
Authors: Albertini et al.
Link to Study: https://doi.org/10.1038/s41593-025-02125-8
Summary
This study reveals how the Alzheimer’s drug Lecanemab works: it activates microglia, immune cells in the brain, to clear amyloid-β (Aβ) plaques, which are a hallmark of Alzheimer’s disease. Using humanized mouse models, researchers showed that Lecanemab triggers a gene program that enhances microglial activity, leading to effective plaque removal and reduced brain damage. This effect relies on the antibody’s Fc region, which interacts with microglia, suggesting a key mechanism for optimizing Alzheimer’s treatments.
Key Takeaways
✅ Lecanemab reduces Aβ plaques in the brain by engaging microglia.
✅ The drug activates specific microglial genes linked to phagocytosis and lysosomal function.
✅ Removing the Fc portion of Lecanemab eliminates its ability to clear plaques—highlighting Fc-microglia interaction as critical.
✅ Lecanemab avoids harmful inflammation and does not cause synaptic loss.
✅ A key protein, osteopontin (SPP1), was found to promote plaque clearance and may play a central role in Lecanemab’s effect.
Why It Matters for You
If you’re concerned about Alzheimer’s, this research helps explain how newer treatments like Lecanemab work, not just by sticking to plaques, but by boosting the brain’s own immune response to clean them up. Supporting microglial health and reducing harmful buildup may be essential steps in preserving memory and cognitive function.
Citation
Albertini, G., Zielonka, M., Cuypers, M.-L., et al. (2025). The Alzheimer’s therapeutic Lecanemab attenuates Aβ pathology by inducing an amyloid-clearing program in microglia. Nature Neuroscience. https://doi.org/10.1038/s41593-025-02125-8