Finally, high level of circulating AChE and metalloproteinases (MMP) have been reported in ALS plasma (61, 62) and although the exact source of these two classes of enzymes remains uncertain, it could in part reflect a disruption of extracellularly bound AChE at the NMJ and early change in the nerve-muscle integrity. The gene discussed is ACHE; the disease is amyotrophic lateral sclerosis.