This research explores how the Alzheimer’s drug Lecanemab utilizes microglia to eliminate harmful amyloid-beta (Aβ) plaques from the brain. By utilizing human microglia xenograft models and spatial transcriptomics, scientists discovered that the therapy’s effectiveness depends on its Fc fragment to trigger a specific genetic program in immune cells. This program boosts phagocytosis, improves lysosomal degradation, and increases the expression of SPP1/osteopontin, a protein that directly aids in clearing deposits. Unlike other treatments, Lecanemab appears to reprogram these cells for a protective response without causing significant synaptic loss or extreme inflammation. Ultimately, the study concludes that effective Aβ reduction requires active microglial engagement, providing a blueprint for refining future immunotherapies.

References:

• Albertini G, Zielonka M, Cuypers M L, et al. The Alzheimer’s therapeutic Lecanemab attenuates Aβ pathology by inducing an amyloid-clearing program in microglia[J]. Nature Neuroscience, 2026, 29(1): 100-110.