APP and amyotrophic lateral sclerosis: Given the fact that a lack of APP can enhance the number of functional synapses in vitro (Priller et al., 2006), presymptomatic expression of APP (in the muscle or the neuron) may initiate synaptic apoptosis at the NMJ in ALS (perhaps due to reactivation of its role in the elimination of multi-innervated synapse during development; (Akaaboune et al., 2000).