Microglia’s Surprising Role in Alzheimer’s Defense

In Alzheimer’s disease, proteins such as amyloid beta can clump into sticky plaques that damage brain cells.In some people, however, the brain’s immune cells—microglia—are able to clear away much of this buildup before it causes serious harm. These individuals tend to have fewer, smaller plaques and experience noticeably milder symptoms.

Figure 1. Immune Cells.

The ADGRG1 Receptor: A Key to Plaque Removal

Researchers at the University of California, San Francisco have identified a molecular receptor that enables microglia to efficiently engulf and break down amyloid beta plaques. The receptor, known as ADGRG1, appears to be critical for keeping the brain clear of these toxic clumps. Figure 1 shows Immune Cells.

In mouse models of Alzheimer’s, the absence of ADGRG1 dramatically reduced the microglia’s ability to remove amyloid beta [1]. This led to rapid plaque buildup, brain tissue degeneration, and declines in learning and memory.

“We think this receptor helps microglia keep the brain healthy over many years,” said Xianhua Piao, MD, PhD, a physician-scientist in UCSF’s Department of Pediatrics.

Gene Expression Clues from Human Brains

When the team revisited earlier gene expression data from human brain studies, they found a striking pattern:

People who died with mild Alzheimer’s had microglia rich in ADGRG1 and showed only mild cognitive impairment—suggesting their microglia were actively clearing plaques.

Those who died with severe Alzheimer’s had very little ADGRG1 in their microglia, allowing plaques to spread unchecked.The findings suggest that boosting ADGRG1 activity could be a potential strategy for slowing or preventing Alzheimer’s progression.

Boosting the Brain’s Defenses

ADGRG1 belongs to a large family of G protein–coupled receptors, a group often targeted in drug development—making this discovery especially promising for turning into new treatments.

“Some people are fortunate to have microglia that do their job well,” said Piao. “But now we have a chance to develop drugs that can make microglia effective at clearing amyloid beta in everyone.”

References:

1. https://scitechdaily.com/some-brains-stay-sharp-thanks-to-a-plaque-eating-immune-cell-that-fights-alzheimers/

Cite this article:

Keerthana S (2025), Plaque-Eating Immune Cells May Help Some Brains Resist Alzheimer’s, AnaTechMaz, pp.449