The amyloid precursor protein (APP) is transported in high amounts to the presynaptic endings where its function is still unknown. Several studies indicate that lack of APP or its overexpression affects the number of dendritic spines, the postsynaptic compartment of excitatory synapses. Since synapse loss has been identified as one of the most important structural correlates of cognitive decline in Alzheimer's diseases (AD), the physiological function of APP at synapses, specifically at dendritic spines, has come into focus in AD research. This review intends to give an overview of the very controversial results on APP expression on dendritic spine number in the mouse brain.