Northwestern University researchers reported a Nature Neuroscience study that maps a peripheral-to-central immune cascade in ALS. The work links early TDP-43 pathology inside motor neurons to subsequent inflammatory immune activity in blood and spinal cord, describing the disease as a “domino-like” sequence. The study combined single-cell RNA sequencing of blood from 40 living ALS patients with spatial transcriptomics in spinal cord tissue from 18 deceased participants, and additional postmortem RNA analyses spanning 237 patients. The authors reported inflammation intensity in the spinal cord as a determinant of progression speed and survival duration. Results also suggest immune profiles vary by ALS subtype and disease stage. The findings support a model in which targeting peripheral immune triggers or the amplification step could influence clinical outcomes and enable more personalized therapy strategies.