The findings we have reported here, together with those by Wang et al., who have proposed that perturbed APP synaptic adhesion activity may contribute to synaptic dysfunction and AD pathogenesis (Wang et al., 2009), reaffirm the NMJ as a versatile and useful experimental model system on which the cell biology of ApoE, APP and ApoE receptor trafficking and its pathobiology at peripheral and central synapses can be investigated. The gene discussed is APP; the disease is Alzheimer disease.