C9orf72 and amyotrophic lateral sclerosis: We also examined the relationship between RNA foci and characteristic neuropathology of C9orf72+ ALS: first, the loss of nuclear TDP-43 in motor neurons, which is the pathological hallmark of ALS (Neumann et al., 2006) and has been shown to correlate with neuronal loss (Brettschneider et al., 2013); and second, the presence of cytoplasmic aggregates containing dipeptide repeat protein, which are a hallmark of C9orf72+ disease (Ash et al., 2013; Mackenzie et al., 2013; Mori et al., 2013b).