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How does ALS spread between neurones in the CNS?
  1. Michael Swash1,2
  1. 1Barts and the London School of Medicine, Queen Mary University of London, London, UK
  2. 2Institute of Molecular Medicine, University of Lisbon, Lisbon, Portugal
  1. Correspondence to Professor Michael Swash, mswash{at}btinternet.com

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In recent years, the concept of contiguous spread of the disease process in amyotrophic lateral sclerosis (ALS) has become more accepted,1 although how this might occur is still uncertain. Kanouchi et al 2 reviewed the extensive clinical, physiological and molecular evidence for this process in this journal, noting that ALS can be recognised to spread both contiguously and non-contiguously, the latter implying more than one focus of disease onset—a ‘skipping’ pattern of spread. They concluded that contiguous spread explains regional progression, but offered no explanation for the process of propagation itself. It has been suggested that cell-to-cell spread requires that abnormal cytosolic proteins in ALS, for example, TDP-43, which seems to underlie the ubiquitinated inclusions so characteristic of sporadic ALS, are misfolded, self-aggregate and form toxic proteinaceous inclusions with a β cross-conformation, resembling prions.3 A prion-like propagation process implies that the abnormal protein spreads to involve other nearby cells, whether neuronal or glial. Prusiner,4 from whose insight the prion …

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