Researchers involving the DQBM Polymenidou Lab identified a distinct Gpnmb-positive microglial state in brain regions undergoing severe cell death in a mouse model of prion disease. Spatial transcriptomics and functional experiments linked this state to increased lysosomal activity and the clearance of apoptotic cells.
The researchers found that soluble signals from dying cells, rather than prion or amyloid aggregates alone, triggered the response. Similar changes appeared in human cell models, stroke models and samples from patients with sporadic Creutzfeldt-Jakob disease. The findings establish a broader mechanism connecting tissue degeneration with microglial activation and suggest that GPNMB may serve as a marker of neurodegeneration.