Whilst these animal studies demonstrate that ALS spreads within MNs that are connected synaptically, a small portion of patients do not display this contiguous spreading of pathology, however. This implies the existence of alternative mechanisms of disease progression (Fujimura-Kiyono et al., 2011; Gargiulo-Monachelli et al., 2012), such as the transfer of misfolded proteins in nanotubules or exosomes (Nonaka et al., 2013; Sundaramoorthy et al., 2013; Grad et al., 2014; Ding et al., 2015; Feiler et al., 2015; Westergard et al., 2016). Interestingly, it has been suggested that the vulnerability of specific MN populations is associated with the spread of neurodegeneration in ALS (Fu et al., 2018).