Overview
- Researchers report a small population of microglia with low PU.1 and CD28 expression that suppress neuroinflammation and slow amyloid and tau pathology.
- Experiments across Alzheimer’s mouse models, human cells, and human brain tissue show that lowering PU.1 induces lymphoid-like receptors on microglia.
- In mice, the protective microglial state preserved cognitive function and improved survival despite its limited numbers.
- Deleting CD28 in this microglial subset heightened inflammation and accelerated plaque growth, demonstrating CD28’s functional role.
- The findings offer a mechanistic explanation for prior SPI1 genetics and position the PU.1–CD28 axis as a preclinical target for microglia-focused immunotherapies.