---

A remarkable discovery may explain why some people seem to have a natural shield against the devastating effects of Alzheimer's disease. Researchers at University of California, San Francisco (UCSF) have identified a specific receptor — named ADGRG1 — that empowers immune cells in the brain, called microglia, to more effectively clear away the sticky amyloid-beta plaques widely believed to drive Alzheimer’s. When microglia are rich in ADGRG1, they appear to protect the brain, slow down the accumulation of toxic plaques, and help preserve memory and cognitive function.

In experiments with mice, the absence of ADGRG1 led to alarmingly rapid plaque buildup, pronounced brain degeneration, and severe impairments in learning and memory. Conversely, when ADGRG1 expression was high, microglia were significantly more efficient at cleaning amyloid deposits, preventing many of the neurodegenerative changes otherwise seen.

Corroborating these findings, analyses of post-mortem human brain tissue revealed a similar pattern: individuals in the early, mild stages of Alzheimer’s often had relatively high levels of ADGRG1 in their microglia, while those with advanced disease showed markedly reduced expression. This suggests that ADGRG1 may play a protective role — or, at least, that losing it could accelerate progression of the disease.

What makes ADGRG1 especially promising is that this receptor belongs to a broader family of G protein-coupled receptors (GPCRs), many of which are already targets of existing drugs — from blood pressure medications to psychiatric treatments. This means there is a realistic possibility of developing therapies designed to boost ADGRG1 function, effectively “supercharging” microglia to defend the brain even in those who are genetically predisposed to Alzheimer’s.

While this approach won’t immediately cure Alzheimer’s, it has the potential to fundamentally shift how the disease is managed: from trying to treat it after symptoms appear, to strengthening the brain’s natural defenses years — or even decades — earlier. If successful, ADGRG1-based therapies could one day slow or prevent the progression of Alzheimer’s over a person’s entire lifetime — a paradigm shift for millions at risk.