New Insights into Microglia's Role in Clearing Amyloid Beta in Alzheimer’s Disease

Research conducted by scientists at the University of California, San Francisco has uncovered a crucial mechanism by which microglia, the brain's immune cells, help combat Alzheimer's disease. In Alzheimer's, abnormal proteins like amyloid beta tend to form sticky clumps called plaques that can damage brain cells and lead to cognitive decline. Interestingly, some individuals naturally possess microglia capable of efficiently degrading these toxic proteins, resulting in fewer and smaller plaques and milder symptoms.

The study identified a specific molecular receptor, ADGRG1, which enables microglia to effectively engulf and break down amyloid beta. In experiments with mouse models lacking this receptor, researchers observed a rapid accumulation of amyloid plaques, increased neurodegeneration, and deficits in learning and memory. Conversely, when the receptor functions properly, microglia help maintain brain health by cleaning up amyloid beta before it causes extensive damage.

Further analysis of human brain tissue revealed that individuals with mild Alzheimer’s had higher levels of ADGRG1 expression in their microglia compared to those with severe Alzheimer’s, indicating a protective role for this receptor in disease progression. Since ADGRG1 is a G protein-coupled receptor, a common target in drug development, this discovery opens new avenues for therapies aimed at boosting microglial activity against amyloid beta.

Dr. Xianhua Piao of UCSF emphasized that this receptor helps microglia perform their vital role in maintaining brain health over many years. This research provides hope that future drugs could enhance microglia’s ability to clear amyloid beta, potentially slowing or preventing the progression of Alzheimer’s disease.

Source: https://medicalxpress.com/news/2025-07-microglia-engulf-amyloid-beta-protein.html