The growing realization that neurotrophins, such as brain-derived neurotrophic factor (BDNF), are crucial in modulating synaptic plasticity has broadened the spectrum of their trophic actions. At the same time, it has become clear that Abeta peptides derived from amyloid precursor protein (APP) have dramatic effects on synaptic transmission before the onset of the neurodegenerative disease. Because neurotrophins and Abeta are responsible for affecting both synaptic and cognitive function, it is likely that their mechanisms of action will be related and might even intersect. This review highlights several recent findings that suggest trophic factors and APP use similar pathways to control neuronal activity.