Amyotrophic lateral sclerosis

Microglial activation and transition to proinflammatory states occurs in ALS spinal cord and motor cortex. SOD1 and TDP-43 mutations, which cause familial ALS, have cell-autonomous effects in microglia that amplify neuronal injury. TREM2, C1QA, C3, and CSF1R are implicated in ALS microglial biology. CSF1R inhibition can slow disease progression in preclinical ALS models. Single-cell RNA-seq of ALS tissue reveals distinct microglial activation states with potential prognostic relevance. The relative contribution of microglial protective versus harmful functions in ALS differs by disease stage.