Researchers at Washington University School of Medicine in St. Louis are making significant strides in the fight against Alzheimer’s disease (AD) by focusing on mobilizing microglia, the brain’s resident immune cells.

Dr. Marco Colonna, the Robert Rock Belliveau Professor of Pathology and Immunology, is leading a study that explores innovative approaches to target harmful amyloid plaques associated with AD. The research suggests that a receptor expressed on the cell surface of microglia could serve as a promising new drug target for the disease.

Microglia are vital in responding to injury or disease, regulating neuronal development, and aiding in the clearance of harmful proteins. However, in AD, these cells exhibit reduced activity. Colonna and his team have identified a specific receptor, known as leukocyte Ig-like receptor B4 (LILRB4), located on microglia near amyloid plaques, which may explain this decreased functionality.

The study found that APOE proteins in plaques bind to LILRB4, inhibiting microglia from effectively controlling plaque formation. To counteract this, the researchers developed a homemade antibody to target LILRB4, blocking the binding of APOE and reducing the number of Aβ plaques in animal models of AD.

In an interview, Colonna highlighted the significance of microglia in AD therapeutics, emphasizing their role in clearing amyloid plaques and impeding disease progression. He also discussed the current landscape of drug development in this space, noting the recent FDA approval of medications targeting beta-amyloid, the primary component of amyloid plaques.

These drugs, monoclonal antibodies, enhance the ability of microglia to detect and reduce amyloid plaques, leading to a moderate slowdown in cognitive decline. While these advancements are promising, Colonna’s research on targeting LILRB4 opens up new possibilities for AD drug development.