As defective PIKfyve function has been shown to cause profound neurodegeneration in mice and in humans [21, 25] and as APP is crucially implicated in Alzheimer's disease we wanted to test whether mutations in apl-1, ppk-3 or vacl-14 can lead to impaired neuronal function in C. elegans. We characterised the overall morphology of the neuronal system of C. elegans using the synaptic marker GFP::RAB-3 by fluorescence microscopy (Fig 6). Here, PIKFYVE is linked to early-onset autosomal dominant Alzheimer disease.