To address the role of the p75NTR in the pathology of Alzheimer’s disease (AD), we started by assessing whether a complete deletion of p75NTR rescues the well-described deficits observed in activity-dependent synaptic plasticity (Chapman et al., 1996; Trinchese et al., 2004) in the hippocampus of APP/PS1 transgenic (APP/PS1tg) mice (Gengler et al., 2010), a commonly used mouse model for AD. This evidence concerns the gene APP and early-onset autosomal dominant Alzheimer disease.