SYP and amyotrophic lateral sclerosis: Shortly after the discovery of SOD1 as the first gene to be linked to ALS, the reduction of the presynaptic marker synaptophysin in the ventral horn of ALS subjects and the depletion of synaptic vesicles in the neuromuscular junction have been shown to be the earliest pathological events in SOD1 G93A mice (149, 150).