Northwestern University Feinberg investigators mapped a peripheral-to-central immune cascade in ALS using integrated single-cell and spatial transcriptomics. In the Nature Neuroscience paper, the study describes a “domino-like” progression in which early pathology inside motor neurons is followed by damaging inflammatory responses involving immune cells in blood and spinal cord. The team analyzed blood from 40 living ALS patients with single-cell RNA sequencing and performed spatial transcriptomics on spinal cord from 18 deceased participants. It also compared immune activity across genetic and non-genetic ALS cohorts and examined RNA from postmortem tissue spanning 237 patients. Researchers reported that the intensity of spinal cord inflammation correlated with disease progression speed and survival. Co-corresponding author David Gate said the study supports the idea that ALS is not a single event but an immune-amplified cascade that may enable more personalized interventions.