Alzheimer’s disease, the most common neurodegenerative disease, is characterized by a progressive loss of synapses and accumulation of amyloid-beta (Aβ) peptides in the brain. Previous studies demonstrated that acute increase in synaptic activity in cultured hippocampal slices and mouse brains (Cirrito et al. Neuron 48: 913–922, 2005; Kamenetz et al. Neuron 37: 925–937, 2003) enhanced secretion of Aβ. Since synaptic activity promotes Aβ secretion, it could also affect the trafficking and processing of its precursor, the amyloid precursor protein (APP). Here, we describe a method to investigate the effect of acute synaptic activation on APP trafficking within dendrites.